DIABETES MELLITUS: AN OVERVIEW

PRACTICE SCHOOL REPORT

Submitted To
RPIIT COLLEGE OF PHARMACY BASTARA
B.PHARMACY7TH SEMESTER
Submitted by
NAME - SAWAN
CLASS- B. PHARMACY 7TH SEMESTER
ROLL NO. – BPH2150

Under the guidance of

Supervisor
Mr PARVINDER
ASSISTANT PROFESSOR

RP EDUCATIONAL TRUST GROUP OF INSTITUTE,

KARNAL (132001)

[Link] UNIVERSITY OF HEALTH SCIENCES,

ROHTAK-124001, HARYANA INDIA
2025
 CERTIFICATE

The work embodied in project work entitled DIABETES MELLITUS‖ is based on my own
project work carried out under the supervision of [Link], Assistant Professor,
Faculty of pharmacy RP Educational Trust Group of Institution, Karnal(Bastara)

Place........................

SAWAN

[Link]
[Link] ( )
Assistant Professor

Faculty of Pharmacy,
RP Educational Trust Group of Institution,
Karnal-132001(HARYANA)

(Supervisor)
 DECLARATION BY THE CANDIDATE

I hereby declare that this thesis entitled DIABETES MELLITUS ‖ is a bonafide and genuine project
work carried out under the supervision of Mr Parvinder , Assistant Professor, Faculty of Pharmacy
RP Educational Trust Group of Institution, Karnal

The present work has not been submitted in part or full for any degree or diploma of this or any other
university.

Place........................

SAWAN

RollNo.BPH2150
 ACKNOWLEDEGEMENT

First, I would like to offer all glory and honour to the Lord for his quick assistance in all my life and
for giving me the strength to work and to conduct my studies.

It is our privilege to express our sincere Regards to our project coordinator, Mr. PARVINDER for
their valuable inputs and guidance and whole-hearted cooperation throughout the project.

We deeply express our sincere thanks to our Head of Department Dr. Prof DIVYA KIRAN for
encouraging and allowing us to present the project on the topic DIABETES MELLITUS.

at our department premises for the partial fulfillment of the requirements leading to the award of B-
Pharmacy degree.

We take this opportunity to thank all our lecturers who have directly or indirectly helped our project.
We pay our respects and love to our parents and all other family members and friends for their love
and encouragement throughout our career. Last but not the least we express our thanks to our friends
for their cooperation and support.

SAWAN

ROLLNO

BPHARMACY
 TABLE OF CONTENT

[Link] TITLES PAGE

NO.

1.

2.

3.
CHAPTER 1
 INTRODUCTION

DIABETES MELLITUS

Diabetes mellitus , or simply diabetes , is a group of metabolic diseases in which a person

has high blood sugar , either because the pancreas does not produce enough insulin , or
because cells do not respond to the insulin that is produced. This high blood sugar produces
the classicals ymptoms of polyuria (frequent urination), polydipsia (increased thirst)
and polyphagia (increased hunger).

There are three main types of diabetes mellitus (DM).

Type 1. DM m the body's failure to produce insulin, and currently requires the person to
inject insulin or wear an insulin pump. This form was previously referred to as "insulin
dependent diabetes mellitus" (IDDM) or "juvenile diabetes".

● Type 2 DM results from insulin resistance , a condition in which cells fail to use insulin
properly, sometimes combined with an absolute insulin deficiency. This form was previously
referred to as non insulin-dependent diabetes mellitus (NIDDM) or"adult-onset diabetes".

● The third main form, gestational diabetes occurs when pregnant women without a
previous diagnosis of diabetes develop a high blood glucose level. It may precede
development of type 2 [Link] forms of diabetes mellitus include congenital diabetes,
which is due to genetic defects of insulin secretion, cystic fibrosis -related diabetes, steroid
diabetes induced by high doses of glucocorticoids, and several forms of monogenic diabetes .

Untreated, diabetes can cause many complications. Acute complications include diabetic
ketoacidosis and nonketotic hyperosmolar coma . Serious long-term complications include
cardiovascular disease , chronic renal failure , and diabetic retinopathy (retinal damage).
Adequate treatment of diabetes is thus important, as well as blood pressure control and
lifestyle factors such as stopping smoking and maintaining a healthy body weight. All forms
of diabetes have been treatable since insulin became available in 1921, and type 2 diabetes
may be controlled with medications. Insulin and some oral medications can
cause hypoglycemia (low blood sugars), which can be dangerous if severe. Both types 1 and
2 are chronic conditions that cannot be cured. Pancreas transplants have been tried with
limited success in type 1 DM; gastric bypass surgery has been successful in many with
morbid obesity and type 2 DM. Gestational diabetes usually resolves after delivery .

Classification

1.1 Type 1 diabetes

1.2 Type 2 diabetes
1.3 Gestational diabetes
1.4 Other types

TYPE 1 DIABETES ( INSULIN DEPENDENT)

Type 1 diabetes mellitus is characterized by loss of the insulin-producing beta cells of the
islets Of Langerhans in the pancreas, leading to insulin deficiency. This type can be further
classified as immune-mediated or idiopathic. The majority of type 1 diabetes is of the
immune-mediated nature, in which beta cell loss is a T-cell -mediated autoimmune attack.
There is no known preventive measure against type 1 diabetes, which causes approximately
10% of diabetes mellitus cases in North America and Europe. Most affected people are
otherwise healthy and of healthy weight when onset occurs. Sensitivity and responsiveness to
insulin are usually normal, especially in the early stages. Type 1 diabetes can affect children
or adults, but was traditionally termed "juvenile diabetes" because a majority of these
diabetes cases were in children.

"Brittle" diabetes, also known as unstable diabetes or labile diabetes, is a term that was
traditionally used to describe to dramatic and recurrent swings in glucose levels, often
occurring for no apparent reason in insulin -dependent diabetes. This term, however, has no
biologic basis and should not be used. There are many reasons for type 1 diabetes to be
accompanied by irregular and unpredictable hyperglycaemia , frequently with ketosis , and
sometimes serious hypoglycaemia, including an impaired counter regulatory response to
hypoglycemia, occult infection, gastroparesis (which leads to erratic absorption of dietary
carbohydrates), and endocrinopathies (e.g., Addison's disease) These phenomena are believed
to occur no more frequently than in 1% to 2% of persons with type 1 diabetetes

TYPE 2 DIABETES

Type 2 diabetes mellitus is characterized by insulin resistance , which may be combined with
relatively reduced insulin secretion. The defective responsiveness of body tissues to insulin is
believed to involve the insulin receptor . However, the specific defects are not known.
Diabetes mellitus cases due to a known defect are classified separately. Type 2 diabetes is the
most common type. In the early stage of type 2, the predominant abnormality is reduced
insulin sensitivity. At this stage, hyperglycemia can be reversed by a variety of measures and
medications that improve insulin sensitivity or reduce glucose production by the liver.

GESTATIONAL DIABETES

Gestational diabetes mellitus (GDM) resembles type 2 diabetes in several respects, involving
a combination of relatively inadequate insulin secretion and responsiveness. It occurs in
about2%–5% of all pregnancies and may improve or disappear after delivery. Gestational
diabetes is fully treatable, but requires careful medical supervision throughout the pregnancy.
About 20%–50% of affected women develop type 2 diabetes later in life.

Though it may be transient, untreated gestational diabetes can damage the health of the fetus
or mother. Risks to the baby include macrosomia (high birth weight), congenital cardiac and
central nervous system anomalies, and skeletal muscle malformations. Increased fetal insulin
may inhibit fetal surfactant production and cause respiratory distress syndrome .

Hyperbilirubinemia may result from red blood cell destruction. In severe cases,prenatal death
may occur, most commonly as a result of poor placental perfusion due to vascular
impairment. Labor induction may be indicated with decreased placental function. A
Caesarean section may be performed if there is marked fetal distress or an increased risk of
injury associated with macrosomia, such as shoulder dystocia.
A 2008 study completed in the U.S. found the number of American women entering
pregnancy with pre-existing diabetes is increasing. In fact, the rate of diabetes in expectant
mothers has more than doubled in the past six years. This is particularly problematic as
diabetes raises the risk of complications during pregnancy, as well as increasing the potential
for the children of diabetic mothers to become diabetic in the future.

OTHER TYPES

Prediabetes indicates a condition that occurs when a person's blood glucose levels are higher
than normal but not high enough for a diagnosis of type 2 DM. Many people destined to
develop type 2 DM spend many years in a state of prediabetes which has been termed
"America's largest healthcare epidemic." Latent autoimmune diabetes of adults (LADA) is a
condition in which type 1 DM develops in adults. Adults with LADA are frequently initially
misdiagnosed as having type 2 DM, based on age rather than etiology. Some cases of
diabetes are caused by the body's tissue receptors not responding to insulin (even
when insulin levels are normal, which is what separates it from type 2 diabetes); this form is
very uncommon. Genetic mutations ( autosomal or mitochondrial ) can lead to defects in beta
cell function. Abnormal insulin action may also have been genetically determined in some
cases. Any disease that causes extensive damage to the pancreas may lead to diabetes (for
example, chronic pancreatitis and cystic fibrosis ). Diseases associated with excessive
secretion of insulin-antagonistic hormones can cause diabetes (which is typically resolved
once the hormone excess is removed). Many drugs impair insulin secretion and some toxins
damage pancreatic beta cells.
CHAPTER 2
 LITERATURE REVIEW

1. Rajaei E, Jalali MT, Shahrabi S, Asnafi AA, Pezeshki SMS(2019). HLAs in

Autoimmune Diseases Since the discovery of HLA 60 years ago, it has contributed to
the understanding of the immune system as well as of the pathogenesis of several
diseases. Aside from its essential role in determining donor-recipient immune
compatibility in organ transplantation, HLA genotyping is meanwhile performed
routinely as part of the diagnostic work-up of certain autoimmune diseases.
Considering the ability of HLA to influence thymic selection as well as peripheral
anergy of T cells, its role in the pathogenesis of autoimmunity is understandable. The
aim of this paper is to provide a brief overview of the role and current clinical
relevance of HLA-B27 in spondyloarthritis and HLA-B51 in Behçet's disease as well
as HLA-DQ2/DQ8 in celiac disease and HLA-DRB1 in rheumatoid arthritis and to
discuss possible future implications.

2. Kühl C(1998). Etiology and pathogenesis of gestational diabetes. Gestational

diabetes mellitus (GDM) is a serious pregnancy complication, in which women
without previously diagnosed diabetes develop chronic hyperglycemia during
gestation. In most cases, this hyperglycemia is the result of impaired glucose tolerance
due to pancreatic β-cell dysfunction on a background of chronic insulin resistance.
Risk factors for GDM include overweight and obesity, advanced maternal age, and a
family history or any form of diabetes. Consequences of GDM include increased risk
of maternal cardiovascular disease and type 2 diabetes and macrosomia and birth
complications in the infant. There is also a longer-term risk of obesity, type 2
diabetes, and cardiovascular disease in the child. GDM affects approximately 16.5%
of pregnancies worldwide, and this number is set to increase with the escalating
obesity epidemic. While several management strategies exist—including insulin and
lifestyle interventions—there is not yet a cure or an efficacious prevention strategy.
One reason for this is that the molecular mechanisms underlying GDM are poorly
defined. This review discusses what is known about the pathophysiology of GDM,
and where there are gaps in the literature that warrant further exploration.
3. Gale EA, Gillespie KM(2001). Diabetes and gender The prevalence of type 2
diabetes mellitus is increasing in both sexes, but men are usually diagnosed at a
younger age and lower body fat mass than women. Worldwide, an estimated 17.7
 million more men than women have diabetes mellitus. Women appear to bear a
greater risk factor burden at the time of their type 2 diabetes diagnosis, especially
obesity. Moreover, psychosocial stress might play a more prominent role in diabetes
risk in women. Across their lifespan, women experience greater hormone fluctuations
and body changes due to reproductive factors than men. Pregnancies can unmask pre-
existing metabolic abnormalities, resulting in the diagnosis of gestational diabetes,
which appears to be the most prominent risk factor for progression to type 2 diabetes
in women. Additionally, menopause increases women's cardiometabolic risk profile.
Due to the progressive rise in obesity, there is a global increase in women with
pregestational type 2 diabetes, often with inadequate preconceptual care. There are
differences between men and women regarding type 2 diabetes and other
cardiovascular risk factors with respect to comorbidities, the manifestation of
complications and the initiation of and adherence to therapy. Women with type 2
diabetes show greater relative risk of CVD and mortality than men. Moreover, young
women with type 2 diabetes are currently less likely than men to receive the treatment
and CVD risk reduction recommended by guidelines. Current medical
recommendations do not provide information on sex-specific or gender-sensitive
prevention strategies and management. Thus, more research on sex differences,
including the underlying mechanisms, is necessary to increase the evidence in the
future. Nonetheless, intensified efforts to screen for glucose metabolism disorders and
other cardiovascular risk factors, as well as the early establishment of prophylactic
measures and aggressive risk management strategies, are still required for both men
and women at increased risk of type 2 diabetes. In this narrative review we aim to
summarise sex-specific clinical features and differences between women and men
with type 2 diabetes into risk factors, screening, diagnosis, complications and
treatment.
4. Carter JS, Pugh JA, Monterrosa( 1996) A. Non-insulin-dependent diabetes mellitus
in minorities in the United States Diabetes shows an increased prevalence among
minority groups, including Asians, African Americans, Hispanics, Native Americans,
and Pacific Islanders. The sedentary lifestyle and high-fat diet of modern
industrialized societies promote obesity at an early age. There is a strong correlation
between the development of diabetes and increased visceral adiposity in American
minority groups. This review focuses on the 2 largest minority groups in the United
States, African Americans and Hispanics. The risk of diabetes is 20% to 50% greater
 in African American men and twice as great in African American women as well as
twice as high in Hispanic adults than in whites. Furthermore, the prevalence of
diabetes-associated complications, such as retinopathy and amputations, is 50% to
100% higher in African Americans and Hispanics.
5. Unger RH, Orci L(2010). Paracrinology of islets and the paracrinopathy of diabetes
New results have brought to light the importance of the regulation of glucagon by β-
cells in the development of diabetes. In this perspective, we examine the normal
paracrinology of α- and β-cells in nondiabetic pancreatic islets. We propose a
Sherringtonian model of coordinated reciprocal secretory responses of these
juxtaposed cells that secrete glucagon and insulin, hormones with opposing actions on
the liver. As insulin is a powerful inhibitor of glucagon, we propose that within-islet
inhibition of α-cells by β-cells creates an insulin-to-glucagon ratio that maintains
glycemic stability even in extremes of glucose influx or efflux. By contrast, in type 1
diabetes mellitus, α-cells lack constant action of high insulin levels from juxtaposed
β-cells. Replacement with exogenous insulin does not approach paracrine levels of
secreted insulin except with high doses that ―overinsulinize‖ the peripheral insulin
targets, thereby promoting glycemic volatility. Based on the stable normoglycemia of
mice with type 1 diabetes during suppression of glucagon with leptin, we conclude
that, in the absence of paracrine regulation of α-cells, tonic inhibition of α-cells
improves the dysregulated glucose homeostasis. These results have considerable
medical implications, as they suggest new approaches to normalize the extreme
volatility of glycemia in diabetic patients.
6. Selph S, Dana T, Bougatsos C(2008),. Screening for Abnormal Glucose and Type 2
Diabetes [Link] one good- and one fair-quality trial, screening for DM was
associated with no mortality benefit versus no screening, including one trial of
patients at higher risk for diabetes (hazard ratio, 1.06 [95% confidence interval, 0.90
to 1.25]). Evidence on harms of screening was limited but indicated no long-term
psychological harms. Consistent evidence from multiple trials found that treatment of
IFG/IGT was associated with delayed progression to DM. Most trials of treatment for
IFG/IGT found no difference in all-cause or cardiovascular mortality, although one
trial found that use of lifestyle modification reduced risk of both outcomes after 23
years followup. For screen-detected diabetes, one large fair-quality trial found no
effect of an intensive multifactorial intervention on risk of all-cause or cardiovascular
mortality versus standard control. For established diabetes (not specifically screen
 detected), intensive glucose treatment was associated with reduced risk of myocardial
infarction and retinopathy, with no effects on mortality. Intensive blood pressure
control was associated with a slightly reduced risk of mortality versus standard
therapy, but evidence from two recent major trials was mixed.
7. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA(2008). 10-year follow-up
of intensive glucose control in type 2 diabetes : During the United Kingdom
Prospective Diabetes Study (UKPDS), patients with type 2 diabetes mellitus who
received intensive glucose therapy had a lower risk of microvascular complications
than did those receiving conventional dietary therapy. We conducted post-trial
monitoring to determine whether this improved glucose control persisted and whether
such therapy had a long-term effect on macrovascular outcomes. Of 5102 patients
with newly diagnosed type 2 diabetes, 4209 were randomly assigned to receive either
conventional therapy (dietary restriction) or intensive therapy (either sulfonylurea or
insulin or, in overweight patients, metformin) for glucose control. In post-trial
monitoring, 3277 patients were asked to attend annual UKPDS clinics for 5 years, but
no attempts were made to maintain their previously assigned therapies. Annual
questionnaires were used to follow patients who were unable to attend the clinics, and
all patients in years 6 to 10 were assessed through questionnaires. We examined seven
prespecified aggregate clinical outcomes from the UKPDS on an intention-to-treat
basis, according to previous randomization categories.
8. Loke YK, Singh S, Furberg CD(2009). Long-term use of thiazolidinediones and
fractures in type2 diabetes: a meta-analysis Rosiglitazone and pioglitazone may
increase the incidence of fractures. We aimed to determine systematically the risk of
fractures associated with thiazolidinedione therapy and to evaluate the effect of the
therapy on bone [Link] searched MEDLINE, EMBASE, the Cochrane Central
Register of Controlled Trials (CENTRAL), other trial registries and product
information sheets through June 2008. We selected long-term (> or = 1 year)
randomized controlled trials involving patients with type 2 diabetes and controlled
observational studies that described the risk of fractures or changes in bone density
with thiazolidinediones. We calculated pooled odds ratios (ORs) for fractures and the
weighted mean difference in bone density.
9. Fajans SS, Bell GI, Polonsky KS(2001). Molecular mechanisms and clinical
pathophysiology of maturity-onset diabetes of the young Maturity-onset diabetes of
the young (MODY) is a clinically heterogeneous group of disorders characterized
 by nonketotic diabetes mellitus, an autosomal dominant mode of inheritance, an
onset usually before the age of 25 years and frequently in childhood or
adolescence, and a primary defect in the function of the beta cells of the pancreas.
MODY can result from mutations in any one of at least six different genes (Table
1). One of these genes encodes the glycolytic enzyme glucokinase (associated
with MODY 2), 3 and the other five encode transcription factors: hepatocyte
nuclear factor (HNF) 4α (associated with MODY 1), 4 HNF-1α (MODY . . .
10. Rush T, McGeary M, Sicignano N, Buryk MA.(2018) A plateau in new onset type 1
diabetes: Incidence of pediatric diabetes in the United States Military Health System
To describe the incidence and prevalence of type 1 diabetes among pediatric
dependents of the US Department of Defense. The Military Health System (MHS)
data repository was used to identify pediatric patients (≤17 years of age) with type 1
diabetes from January 1, 2007 to December 31, 2012. Annual incidence, annual
prevalence and adjusted incidence were calculated and stratified by sex, age group,
and region of [Link] a 6-year study period from 2007 to 2012, 5616
pediatric patients with type 1 diabetes were identified; 57% male, mean (SD) age of
10.9 (4.2) years. Annual type 1 diabetes incidence (per 100 000 persons) over the 5-
year time period ranged from 20.7/100 000 to 21.3/100 000. Incidence for each year
was highest in the 10 to 14 years age group and ranged from 30.9/100 000 in 2008 to
35.2/100 000 in 2011. Annual type 1 diabetes prevalence (per 1000 persons) remained
stable throughout the study period at 1.5/1000. Adjusted incidence for males was
significantly higher compared to females (21.0/100 000 vs 18.1/100 000; P = .001).
During the study period, annual incidence remained steady (test for trend, P =
.984). The incidence of type 1 diabetes among children appears to plateau during the
study period, suggesting a steady state of type 1 diabetes within this pediatric
population. The MHS provides an accurate and up to date look at incidence of type 1
diabetes and may reflect broader trends of incidence of pediatric disease for the
United States as a whole.
11. Zheng Y, Ley SH, Hu FB(2018). Global aetiology and epidemiology of type 2
diabetes mellitus and its complications. Globally, the number of people with diabetes
mellitus has quadrupled in the past three decades, and diabetes mellitus is the ninth
major cause of death. About 1 in 11 adults worldwide now have diabetes mellitus,
90% of whom have type 2 diabetes mellitus (T2DM). Asia is a major area of the
rapidly emerging T2DM global epidemic, with China and India the top two
 epicentres. Although genetic predisposition partly determines individual susceptibility
to T2DM, an unhealthy diet and a sedentary lifestyle are important drivers of the
current global epidemic; early developmental factors (such as intrauterine exposures)
also have a role in susceptibility to T2DM later in life. Many cases of T2DM could be
prevented with lifestyle changes, including maintaining a healthy body weight,
consuming a healthy diet, staying physically active, not smoking and drinking alcohol
in moderation. Most patients with T2DM have at least one complication, and
cardiovascular complications are the leading cause of morbidity and mortality in these
patients. This Review provides an updated view of the global epidemiology of T2DM,
as well as dietary, lifestyle and other risk factors for T2DM and its complications.
12. Klein BE, Klein R, Moss SE, Cruickshanks KJ. Parental history of diabetes in a
populationbased study. o evaluate the relative frequency of parental history of
diabetes in a population-based study of younger- and older-onset groups of
individuals with diabetes and a comparison group of individuals without
[Link] participants were queried about a family history of diabetes. The
frequencies of positive responses for parents and siblings were compared between
younger- and older-onset groups. At least one parent had diabetes in 18.6% of the
families of younger-onset individuals and in 38.6% of the families of older-onset
individuals. For those of younger-onset diabetes, 9.1% of fathers, 8.3% of mothers,
and 1.3% of both parents had diabetes; the corresponding percentage for those of
older-onset diabetes were 11.5, 23.5, and 3.6%, respectively. The difference between
frequencies in mothers and fathers was significant (P < 0.0001) in the older-onset
group. In the nondiabetic comparison group, for those of similar ages to the younger-
and older-onset groups, the corresponding frequencies were 6.2 and 9.0% and 7.7 and
9.8% for fathers and mothers, respectively. The greater frequencies of diabetes in
mothers of older-onset diabetic individuals were not accounted for by maternal age. In
younger-onset individuals, the relative risk (RR) of diabetes in a sibling if the father
had diabetes was 1.22 (95% CI, 0.72-2.05); if the mother had diabetes, the RR was
2.39 (95% CI, 1.64-3.48); and, if both parents had diabetes, the RR was 5.61 (95% CI,
3.37-9.34). In the older-onset individuals, the corresponding RR values were 1.69
(95% CI, 1.35-2.13) for fathers, 1.72 (95% CI, 1.44-2.06) for mothers, and 2.42 (95%
CI, 1.81-3.25) for both [Link] data confirm a familial influence on the
frequency of diabetes. The excess of cases in mothers of older-onset diabetic
individuals is compatible with both environmental and genetic influences.
13. Barnett AH, Eff C, Leslie RD, Pyke DA. Diabetes in identical twins. A study of 200
pairs. Of 96 pairs of identical twins, 65 were concordant (both diabetic) and 31
discordant (one twin diabetic). When diabetes developed in the index twin before the
age of 40 half the pairs were discordant, whereas in twins in whom diabetes
developed after the age of 40 almost all pairs were concordant. In 75% of concordant
twins the interval between diagnoses was under 3 years. It is suggested that the
unaffected twins of the discordant pairs will probably remain non-diabetic, since half
the pairs had been discordant for over 10 years, and most had a normal glucose
tolerance which had not deteriorated. The concordant diabetics showed the usual
tendency to produce heavy babies before they became diabetic, but the unaffected
twins did not. A family history of diabetes was common in concordant twins and rare
in discordant twins. Diabetes in discordant twins may be mainly environmentally
determined, although obesity, diet, parity, or other ætiological factors have not been
incriminated, and the unaffected identical twins of diabetics are not "prediabetics".
14. Vehik K, Hamman RF, Lezotte D, Norris JM, Klingensmith G, Bloch C, Rewers M,
Dabelea D. Increasing incidence of type 1 diabetes in 0- to 17-year-old Colorado
youth We sought to assess the long-term trends in the incidence of type 1 diabetes
among non-Hispanic white and Hispanic youth aged 0-17 years from Colorado using
data from the Colorado IDDM Study Registry (1978-1988) and SEARCH for
Diabetes in Youth (2002-2004). Cases of diabetes were ascertained through physician
reporting and hospital databases. Type 1 diabetes was defined as use of insulin within
2 weeks from diagnosis. Completeness of ascertainment was estimated as 97%.
Annual average incidence rates (per 100,000/year) and 95% CIs for the time periods
were computed. Trends in incidence were assessed by Poisson regression. The
incidence of type 1 diabetes was 14.8 (95% CI 14.0-15.6) in 1978-1988 and 23.9
(22.2-25.6) in 2002-2004 for the state of Colorado (P < 0.0001). From 1978 to 2004,
the incidence of type 1 diabetes increased by 2.3% (1.6-3.1) per year (P < 0.0001).
The increase in incidence was significant for both non-Hispanic white (2.7% [95% CI
1.9-3.6] per year, P < 0.0001) and Hispanic youth (1.6% [0.2-3.1] per year, P =
0.013). The incidence of type 1 diabetes has increased 1.6-fold among Colorado youth
from 1978-1988 to 2002-2004, and both non-Hispanic white and Hispanic youth are
affected by this trend.
15. Shim K, Gulhar R, Jialal I. Exploratory metabolomics of nascent metabolic syndrome
Metabolic syndrome (MetS) is a disorder defined by having three of five features:
 increased waist circumference (WC), hypertriglyceridemia, decreased high-density
lipoprotein-cholesterol, hypertension and an elevated blood glucose (BG). Metabolic
Syndrome ( MetS) affects 35% of American adults and significantly increases risk for
Atherosclerotic cardiovascular disease (ASCVD) and type-2 diabetes (T2DM). An
understanding of the metabolome will help elucidate the pathogenesis of MetS and
lead to better management. We hypothesize that the metabolites, gamma-
aminobutyric acid (GABA), d-pyroglutamic acid (PGA) and N-acetyl-d-tryptophan
(NAT) will be altered in nascent MetS patients without the confounding of ASCVD
or T2DM. We also correlated these metabolites with biomarkers of
inflammation. This was an exploratory study of 30 patients with nascent MetS and 20
matched controls undertaken in 2018. Metabolites were evaluated from patient's
frozen early morning urine samples and were correlated with biomarkers of
inflammation and adipokines. They were assayed by the NIH Western Metabolomics
Center using liquid chromatography/mass spectrometry and standardized to urinary
creatinine. All patients had normal hepatic and renal [Link] and PGA levels
were significantly increased in MetS patients compared to controls: 2.8-fold and 2.9-
fold median increases respectively with p < 0.0001 and p = 0.004, possibly deriving
from glutamate. NAT was significantly decreased by 90% in MetS patients compared
to controls, p < 0.001. GABA correlates significantly with cardio-metabolic (CM)
features including WC, blood pressure systolic (BP-S) while NAT correlated
inversely with WC, BP-S, blood glucose (BG) and triglycerides (TG). GABA
correlated positively with chemerin, leptin, Fetuin A and endotoxin. NAT correlated
inversely with WC, BP-S, BG, TG, high sensitivity C - reactive protein (hsCRP), toll-
like receptor-4 (TLR-4), lipopolysaccharide binding protein (LBP), chemerin and
retinol binding protein-4 (RBP-4).
16. Forbes JM, Cooper ME. Mechanisms of diabetic complications It is increasingly
apparent that not only is a cure for the current worldwide diabetes epidemic required,
but also for its major complications, affecting both small and large blood vessels.
These complications occur in the majority of individuals with both type 1 and type 2
diabetes. Among the most prevalent microvascular complications are kidney disease,
blindness, and amputations, with current therapies only slowing disease progression.
Impaired kidney function, exhibited as a reduced glomerular filtration rate, is also a
major risk factor for macrovascular complications, such as heart attacks and strokes.
There have been a large number of new therapies tested in clinical trials for diabetic
 complications, with, in general, rather disappointing results. Indeed, it remains to be
fully defined as to which pathways in diabetic complications are essentially protective
rather than pathological, in terms of their effects on the underlying disease process.
Furthermore, seemingly independent pathways are also showing significant
interactions with each other to exacerbate pathology. Interestingly, some of these
pathways may not only play key roles in complications but also in the development of
diabetes per se. This review aims to comprehensively discuss the well validated, as
well as putative mechanisms involved in the development of diabetic complications.
In addition, new fields of research, which warrant further investigation as potential
therapeutic targets of the future, will be highlighted.
17. Stern MP. Do non-insulin-dependent diabetes mellitus and cardiovascular disease
share common antecedents Recent evidence suggests that non-insulin-dependent
diabetes mellitus (NIDDM) and cardiovascular disease, rather than being related as
underlying disease and complication, share common genetic and environmental
antecedents, that is, they "spring from the same soil." Fetal and early-life nutritional
deficiencies appear to predispose persons to both NIDDM and cardiovascular disease
in later life. The insulin resistance syndrome, including abdominal obesity, may
constitute the intermediate link between fetal and early-life nutritional deficiency and
later disease. The insulin resistance syndrome includes insulin resistance,
hyperinsulinemia, abdominal obesity, dyslipidemia with high triglyceride and low
high-density lipoprotein cholesterol levels, and hypertension. Each element of the
insulin resistance syndrome has been firmly established as a risk factor for
development of diabetes. In addition, most of these elements are also well-recognized
cardiovascular risk factors, although the weight of evidence now suggests that
hyperinsulinemia itself is not. This last point is significant because of concern that
aggressive insulinization of diabetic patients, which has been proved to reduce
microvascular complications, might paradoxically increase the risk for large-vessel
atherosclerosis. Available clinical trials suggest that this fear is unwarranted, but
definitive trials are needed to resolve this important clinical question.
CHAPTER 3
 AIM AND OBJECTIVE

The objective of addressing diabetes mellitus can vary depending on the context—medical
treatment, research, education, or public health. Below are general and specific objectives
categorized accordingly

1. General Medical Objective:

To effectively manage and control blood glucose levels in individuals diagnosed with
diabetes mellitus in order to prevent both acute and chronic complications.

2. Clinical Objectives:

To achieve and maintain optimal glycemic control (fasting blood glucose, postprandial
glucose, and HbA1c levels). To prevent or delay the onset of complications such as
neuropathy, nephropathy, retinopathy, and cardiovascular diseases. To improve the quality of
life of individuals with diabetes through patient-centered care and regular follow-up. To
individualize treatment plans based on type (Type 1 or Type 2), age, lifestyle, comorbidities,
and other factors.

3. Public Health Objectives:

To raise awareness about the risk factors and early signs of diabetes. To promote lifestyle
modifications (healthy diet, regular exercise, weight management) to prevent Type 2
diabetes. To enhance accessibility to screening, diagnosis, and treatment services in both
urban and rural areas. To reduce the overall prevalence and economic burden of diabetes on
the healthcare system.

4. Research Objectives:

To identify the genetic, environmental, and immunologic factors contributing to the

development of diabetes. To develop innovative treatment modalities, including new drugs,
insulin delivery systems, and potential cures. To evaluate the long-term outcomes of current
treatment approaches and patient management strategies. To investigate prevention strategies,
especially for high-risk populations.
5. Educational Objectives (for patients and healthcare providers):

To educate patients on self-monitoring of blood glucose (SMBG), insulin administration, and

managing hypoglycemia. To train healthcare providers on the latest guidelines and
technologies in diabetes management. To encourage adherence to prescribed medications,
dietary plans, and follow-up appointments.
CHAPTER 4
 PROJECT DESIGN AND CASE STUDY

ETIOLOGY

In the islets of Langerhans in the pancreas, there are two main subclasses of endocrine cells:
insulin-producing beta cells and glucagon secreting alpha cells. Beta and alpha cells are
continually changing their levels of hormone secretions based on the glucose environment.
Without the balance between insulin and glucagon, the glucose levels become inappropriately
skewed. In the case of DM, insulin is either absent and/or has impaired action (insulin
resistance), and thus leads to hyperglycemia

T1DM is characterized by the destruction of beta cells in the pancreas, typically secondary to
an autoimmune process. The result is the absolute destruction of beta cells, and
consequentially, insulin is absent or extremely low. T2DM involves a more insidious onset
where an imbalance between insulin levels and insulin sensitivity causes a functional deficit
of insulin. Insulin resistance is multifactorial but commonly develops from obesity and aging

The genetic background for both types is critical as a risk factor. As the human genome gets
further explored, there are different loci found that confer risk for DM. Polymorphisms have
been known to influence the risk for T1DM, including major histocompatibility complex
(MHC) and human leukocyte antigen (HLA).[1]
T2DM involves a more complex interplay between genetics and lifestyle. There is clear
evidence suggesting that T2DM is has a stronger hereditary profile as compared to T1DM.
The majority of patients with the disease have at least one parent with T2DM.[2]
Monozygotic twins with one affected twin have a 90% likelihood of the other twin
developing T2DM in his/her lifetime.[3] Approximately 50 polymorphisms to date have been
described to contribute to the risk or protection for T2DM. These genes encode for proteins
involved in various pathways leading to DM, including pancreatic development, insulin
synthesis, secretion, and development, amyloid deposition in beta cells, insulin resistance,
and impaired gluconeogenesis regulation. A genomewide association study (GWAS) found
genetic loci for transcription factor 7- like 2 gene (TCF7L2), which increases the risk for
T2DM.[4][5] Other loci that have implications in the development of T2DM include
NOTCH2, JAZF1, KCNQ1, and WFS1.[6][7]

MODY is a heterogeneous disorder identified by non-insulin-dependent diabetes diagnosed at

a young age (usually under 25 years). It carries an autosomal dominant transmission and does
not involve autoantibodies as in T1DM. Several genes have implications in this disease,
including mutations to hepatocyte nuclear factor-1-alpha (HNF1A) and the glucokinase
(GCK) gene, which occurs in 52 to 65 and 15 to 32 percent of MODY cases,
respectively.[8][9] Gestational diabetes is essentially diabetes that manifests during
pregnancy. It is still unknown why it develops; however, some speculate that HLA antigens
may play a role, specifically HLA DR2, 3, and 4. Excessive proinsulin is also thought to play
a role in gestational diabetes, and some suggest that proinsulin may induce beta-cell stress.
Others believe that high concentrations of hormones such as progesterone, cortisol, prolactin,
human placental lactogen, and estrogen may affect beta-cell function and peripheral insulin
sensitivity.[10] Several endocrinopathies, including acromegaly, Cushing syndrome,
glucagonoma, hyperthyroidism, hyperaldosteronism, and somatostatinomas, have been
associated with glucose intolerance and diabetes mellitus, due to the inherent glucogenic
action of the endogenous hormones excessively secreted in these conditions. Conditions like
idiopathic hemochromatosis are associated with diabetes mellitus due to excessive iron
deposition in the pancreas and the destruction of the beta cells.
 EPIDEMILOGY

Globally, 1 in 11 adults has DM (90% having T2DM). The onset of T1DM gradually
increases from birth and peaks at ages 4 to 6 years and then again from 10 to 14 years.[11]
Approximately 45% of children present before age ten years.[12] The prevalence in people
under age 20 is about 2.3 per 1000. While most autoimmune diseases are more common in
females, there are no apparent gender differences in the incidence of childhood T1DM. In
some populations, such as in older males of European origin (over 13 years), they may be
more likely to develop T1DM compared to females (3:2 male to female ratio).[13] The
incidence of T1DM has been increasing worldwide. In Europe, Australia, and the Middle
East, rates are rising by 2% to 5% annually.[14][15][16] In the United States, T1DM rates
rose in most age and ethnic groups by about 2% yearly, and rates are higher in Hispanic
youth.[17] The exact reason for this pattern remains unknown. However, some metrics, such
as the United States Military Health System data repository, found plateauing over 2007 to
2012 with a prevalence of 1.5 per 1000 and incidence of 20.7 to 21.3 per 1000.[18]

The onset of T2DM is usually later in life, though obesity in adolescents has led to an
increase in T2DM in younger populations. T2DM has a prevalence of about 9% in the total
population of the United States, but approximately 25% in those over 65 years. The
International Diabetes Federation estimates that 1 in 11 adults between 20 and 79 years had
DM globally in 2015. Experts expect the prevalence of DM to increase from 415 to 642
million by 2040, with the most significant increase in populations transitioning from low to
middle-income levels.[19] T2DM varies among ethnic groups and is 2 to 6 times more
prevalent in Blacks, Native Americans, Pima Indians, and Hispanic Americans compared to
Whites in the United States.[20][21] While ethnicity alone plays a vital role in T2DM,
environmental factors also greatly confer risk for the disease. For example, Pima Indians in
Mexico are less likely to develop T2DM compared to Pima Indians in the United States
(6.9% vs. 38%).[22]
 PATHOPHYSIOLOGY

A patient with DM has the potential for hyperglycemia. The pathology of DM can be unclear
since several factors can often contribute to the disease. Hyperglycemia alone can impair
pancreatic beta-cell function and contributes to impaired insulin secretion. Consequentially,
there is a vicious cycle of hyperglycemia leading to an impaired metabolic state. Blood
glucose levels above 180 mg/dL are often considered hyperglycemic in this context, though
because of the variety of mechanisms, there is no clear cutoff point. Patients experience
osmotic diuresis due to saturation of the glucose transporters in the nephron at higher blood
glucose levels. Although the effect is variable, serum glucose levels above 250 mg/dL are
likely to cause symptoms of polyuria and polydipsia.

Insulin resistance is attributable to excess fatty acids and proinflammatory cytokines, which
leads to impaired glucose transport and increases fat breakdown. Since there is an inadequate
response or production of insulin, the body responds by inappropriately increasing glucagon,
thus further contributing to hyperglycemia. While insulin resistance is a component of
T2DM, the full extent of the disease results when the patient has inadequate production of
insulin to compensate for their insulin resistance .

Chronic hyperglycemia also causes nonenzymatic glycation of proteins and lipids. The extent
of this is measurable via the glycation hemoglobin (HbA1c) test. Glycation leads to damage
in small blood vessels in the retina, kidney, and peripheral nerves. Higher glucose levels
hasten the process. This damage leads to the classic diabetic complications of diabetic
retinopathy, nephropathy, and neuropathy and the preventable outcomes of blindness,
 HISTORY AND PHYSICAL

During patient history, questions about family history, autoimmune diseases, and insulin-
resistant are critical to making the diagnosis of DM. It often presents asymptomatically, but
when symptoms develop, patients usually present with polyuria, polydipsia, and weight loss.
On physical examination of someone with hyperglycemia, poor skin turgor (from
dehydration) and a distinctive fruity odor of their breath (in patients with ketosis) may be
present. In the setting of diabetic ketoacidosis (DKA), clinicians may note Kussmaul
respirations, fatigue, nausea, and vomiting. Funduscopic examination in a patient with DM
may show hemorrhages or exudates on the macula. In frank diabetic retinopathy, retinal
venules may appear dilated or occluded. The proliferation of new blood vessels is also a
concern for ophthalmologists and can hasten retinal hemorrhages and macular edema,
ultimately resulting in blindness. While T1DM and T2DM can present similarly, they can be
distinguished based on clinical history and examination. T2DM patients are typically
overweight/obese and present with signs of insulin resistance, including acanthosis nigricans,
which are hyperpigmented, velvety patches on the skin of the neck, axillary, or inguinal folds.
Patients with a longer course of hyperglycemia may have blurry vision, frequent yeast
infections, numbness, or neuropathic pain. The clinicians must ask the patient bout any recent
skin changes in their feet during each visit. The diabetic foot exam, including the
monofilament test, should be a part of the routine physical exam
 EVALUATION

The diagnosis of T1DM is usually through a characteristic history supported by elevated

serum glucose levels (fasting glucose greater than 126 mg/dL, random glucose over 200
mg/dL, or hemoglobin A1C (HbA1c exceeding 6.5%) with or without antibodies to glutamic
acid decarboxylase (GAD) and insulin.

Fasting glucose levels and HbA1c testing are useful for the early identification of T2DM. If
borderline, a glucose tolerance test is an option to evaluate both fasting glucose levels and
serum response to an oral glucose tolerance test (OGTT). Prediabetes, which often precedes
T2DM, presents with a fasting blood glucose level of 100 to 125 mg/dL or a 2-hour post-oral
glucose tolerance test (post-OGTT) glucose level of 140 to 200 mg/dL.[24][25]

According to the American Diabetes Association (ADA), a diagnosis of diabetes is through

any of the following: An HbA1c level of 6.5% or higher; A fasting plasma glucose level of
126 mg/dL (7.0 mmol/L) or higher (no caloric intake for at least 8 hours); A two-hour plasma
glucose level of 11.1 mmol/L or 200 mg/dL or higher during a 75-g OGTT; A random
plasma glucose of 11.1 mmol/L or 200 mg/dL or higher in a patient with symptoms of
hyperglycemia (polyuria, polydipsia, polyphagia, weight loss) or hyperglycemic crisis.[24]
The ADA recommends screening adults aged 45 years and older regardless of risk, while the
United States Preventative Service Task Force suggests screening individuals between 40 to
70 years who are overweight.[26].

To test for gestational diabetes, all pregnant patients have screening between 24 to 28 weeks
of gestation with a 1-hour fasting glucose challenge test. If blood glucose levels are over
140mg/dL, patients have a 3-hour fasting glucose challenge test to confirm a diagnosis. A
positive 3-hours OGTT test is when there is at least one abnormal value (greater than or equal
to 180, 155, and 140 mg/dL for fasting one-hour, two-hour, and 3-hour plasma glucose
concentration, respectively).[27]

Several lab tests are useful in the management of chronic DM. Home glucose testing can
show trends of hyper- and hypoglycemia. The HbA1c test indicates the extent of glycation
due to hyperglycemia over three months (the life of the red blood cell). Urine albumin testing
can identify the early stages of diabetic nephropathy. Since patients with diabetes are also
prone to cardiovascular disease, serum lipid monitoring is advisable at the time of diagnosis.
Similarly, some recommend monitoring thyroid status by obtaining a blood level of thyroid-
stimulating hormone annually due to a higher incidence of hypothyroidism.[24][25]

TREATMENT / MANAGEMENT

The physiology and treatment of diabetes are complex and require a multitude of
interventions for successful disease management. Diabetic education and patient engagement
are critical in management. Patients have better outcomes if they can manage their diet
(carbohydrate and overall caloric restriction), exercise regularly (more than 150 minutes
weekly), and independently monitor glucose.[28] Lifelong treatment is often necessary to
prevent unwanted complications. Ideally, glucose levels should be maintained at 90 to 130
mg/dL and HbA1c at less than 7%. While glucose control is critical, excessively aggressive
management may lead to hypoglycemia, which can have adverse or fatal outcomes.

Since T1DM is a disease primarily due to the absence of insulin, insulin administration
through daily injections, or an insulin pump, is the mainstay of treatment. In T2DM, diet and
exercise may be adequate treatments, especially initially. Other therapies may target insulin
sensitivity or increase insulin secretion by the pancreas. The specific subclasses for drugs
include biguanides (metformin), sulfonylureas, meglitinides, alpha-glucosidase inhibitors,
thiazolidinediones, glucagonlike-peptide-1 agonist, dipeptidyl peptidase IV inhibitors (DPP-
4), selective, amylinomimetics, and sodiumglucose transporter-2 (SGLT-2) inhibitors.
Metformin is the first line of the prescribed diabetic medications and works by lowering basal
and postprandial plasma glucose. Insulin administration may also be necessary for T2DM
patients, especially those with inadequate glucose management in the advanced stages of the
disease. In morbidly obese patients, bariatric surgery is a possible means to normalize
glucose levels. It is recommended for individuals who have been unresponsive to other
treatments and who have significant comorbidities.[29] The GLP-1 agonists liraglutide and
semaglutide correlate with improved cardiovascular outcomes. The SGLT-2 inhibitors
empagliflozin and canagliflozin have also shown to improve cardiovascular outcomes along
with potential renoprotection as well as prevention for the development of heart failure.

Regular screenings are necessary since microvascular complications are a feared

complication of diabetes. Regular diabetic retinal exams should be performed by qualified
medical personnel to assess for diabetic retinopathy. Neurologic examination with
monofilament testing can identify patients with neuropathy at risk for amputation. Clinicians
can also recommend patients perform daily foot inspections to identify foot lesions that may
go unnoticed due to neuropathy. Low-dose tricyclic antidepressants, duloxetine,
anticonvulsants, topical capsaicin, and pain medications may be necessary to manage
neuropathic pain in diabetes. Urine microalbumin testing can also assess for early renal
changes from diabetes with albuminuria greater than 30mg/g creatinine along with the
estimated GFR. The antiproteinuric effect of the angiotensin-converting enzyme (ACE)
inhibitors and the angiotensin receptor blockers (ARBs) makes them the preferred agents to
delay the progression from microalbuminuria to macroalbuminuria in patients with both Type
1 or Type 2 diabetes mellitus. The FDA has approved pregabalin and duloxetine for the
treatment of diabetic peripheral neuropathy. Tricyclic antidepressants and anticonvulsants
have also seen use in the management of the pain of diabetic neuropathy with variable
success.

The ADA also recommends regular blood pressure screening for diabetics, with the goal
being 130 mmHg systolic blood pressure and 85 mmHg diastolic blood pressure.[30]
Pharmacologic therapy for hypertensive diabetics typically involves angiotensin-converting
enzyme inhibitors, angiotensin receptor blockers, diuretics, beta-blockers, and/or calcium
channel blockers. The ADA recommends lipid monitoring for diabetics with a goal of low-
density lipoprotein cholesterol (LDL-C) being less than 100 mg/dL if no cardiovascular
disease (CVD) and less than 70 mg/dl if atherosclerotic cardiovascular disease (ASCVD) is
present. Statins are the first-line treatment for the management of dyslipidemia in diabetics.
The ADA suggests that low dose aspirin may also be beneficial for diabetic patients who are
at high risk for cardiovascular events; however, the role of aspirin in reducing cardiovascular
events in patients with diabetes remains unclear.[31][32][33]
 DIFFERENTIAL DIAGNOSIS

In addition to T1DM, T2DM, and MODY, any disorder that damages the
pancreas can result in DM. There are several diseases of the exocrine
pancreas, including:[34]

• Cystic fibrosis

• Hereditary hemochromatosis

• Pancreatic cancer

• Chronic pancreatitis

Hormonal syndromes that can lead to impaired insulin secretion include:

• Pheochromocytoma

• Acromegaly

• Cushing syndrome

Drug-induced insulin resistance is also in the differential of classical

diabetes. These drugs include:

• Phenytoin

• Glucocorticoids

• Estrogen

Other diseases in the differential of diabetes mellitus include:

• Gestational diabetes[10] • Thyroid disorders
 TOXICITY & ADVERSE EFFECT
MANAGEMENT

One of the most common adverse effects of insulin is hypoglycemia. Gastrointestinal upset is
the most common side effect of many of the T2DM medications. Metformin can lead to lactic
acidosis and should be used with caution in patients with renal disease and discontinued if the
estimated glomerular filtration rate (e-GFR) is under 30 mL/min. Sulfonylureas can lead to
hypoglycemia and may promote cardiovascular death in patients with diabetes.[35]
Thiazolidinediones have fallen out of favor in clinical practice due to their adverse effects,
specifically resulting in fluid retention, worsening heart failure, and fractures.[36][37] DPP-4
may increase the risk for upper respiratory tract infections but may have less nausea and
diarrhea compared to other drugs such as metformin.[38][39] SGLT-2 inhibitors can lead to
increased urinary tract infections due to increased urinary glucose excretion.[40] Both
SGLT2 inhibitors and GLP-1 Receptor agonists reduce ASCVD events and are now
considered the second line to metformin in such patients.

PROGNOSIS

Diabetes mellitus was the seventh leading cause of death in the United States in
2015.[41] The prognosis of DM gets significantly influenced by the degree of
glucose management. Chronic hyperglycemia significantly increases the risk of
DM complications. The Diabetes Control and Complications Trial and the
United Kingdom Prospective Diabetes Study found that individuals with T1DM
and T2DM respectively had increased microvascular complications with
chronic hyperglycemia.[42][43] Patients who can revert to normal glucose
during the progression from pre-diabetes to frank DM had a good prognosis and
may be able to slow disease progression.[44]
 COMPLICATIONS

Regardless of the specific type of diabetes, complications involvemicrovascular,

macrovascular, and neuropathic issues. Microvascular and macrovascular complications vary
according to the degree and the duration of poorly control diabetes and include nephropathy,
retinopathy, neuropathy, and ASCVD events, especially if it is associated with other
comorbidities like dyslipidemia and hypertension.[45] One of the most devastating
consequences of DM is its effect on cardiovascular disease (ASCVD). Approximately two-
thirds of those with DM will die from a myocardial infarction or stroke.[46] In T2DM,
fasting glucose of more than 100 mg/Dl significantly contributes to the risk of ASCVD, and
cardiovascular risk can develop before frank hyperglycemia.[47][48]
DM is also a common cause of blindness in adults aged 20 to 74 years in the United States.
Diabetic retinopathy contributes to 12000 to 24000 new cases of blindness annually, and
treatments generally consist of laser surgery and glucose control.[49]
DM is also a common cause of blindness in adults aged 20 to 74 years in the United States.
Diabetic retinopathy contributes to 12000 to 24000 new cases of blindness annually, and
treatments generally consist of laser surgery and glucose control.[49] Renal disease is another
significant cause of morbidity and mortality in DM patients. It is the leading contributor to
end-stage renal disease (ESRD) in the United States, and many patients with ESRD will need
to start dialysis or receive a kidney transplant.[49] If the albuminuria persists in the range of
30 to 300 mg/day (microalbuminuria), it seems to be a predictable earliest marker for the
onset of diabetic neuropathy. Once macroalbuminuria (greater than 300 mg/24 hr) sets in, the
progression to ESRD hastens up. The random spot urine specimen for measurement of the
albumin-to-creatinine ratio is a quick, easy, predictable method that is the most widely used
and preferred method to detect microalbuminuria. Two of three tests, done over a six month
showing a persistent level greater than 30 mcg/mg creatinine, confirms the diagnosis of
microalbuminuria.
The duration of diabetes is the most crucial risk factor for the development
of diabetic retinopathy. In people with type 1 diabetes, it typically sets in about 5 years after
disease onset. Hence it is recommended to start the yearly retinal exams in these patients
about five years after diagnosis. Among patients with type 2 diabetes, many patients might
already have retinal changes at the time of diagnosis. Approximately 10% at ten years, 40%
at 15 years, and 60% at 20 years will have nonproliferative retinal disease. In these patients,
the recommendation is to start the yearly retinal screening at the time of diagnosis. Study
after study has shown that reasonable glycemic control favorably affected the onset and
progression of diabetic retinopathy. Uncontrolled blood pressure is an added risk factor for
macular edema. Lowering the blood pressure in patients with diabetes thus also affects the
risk of progression of the retinopathy. Injection of antibodies vascular endothelial growth
factor (anti-VEGF) agents are generally in use as the initial therapy in cases of macular
edema. In cases of nonproliferative diabetic retinopathy, pan-retinal photocoagulation is
being used. In cases of diabetic proliferative retinopathy, combined modalities of anti-VEGF
agents and pan-retinal photocoagulation are now in use. Sudden loss of vision can occur for
several reasons in patients with diabetes mellitus, the most common being vitreous
hemorrhage. Less common causes that merit consideration include vascular occlusion
(central retinal vein or branch vein occlusion involving the macula), retinal detachment, end-
stage glaucoma, and ischemic optic neuropathy.
Furthermore, evidence suggests that T2DM may also contribute to cancer development,
specifically bladder cancer, in those using pioglitazone.[50] Patients using metformin had
improved cancer-specific survival in those with prostate, pancreatic, breast, and colorectal
cancers. However, it is unclear how metformin plays a role in modulating cancer in patients
with diabetes.[51]
Those with gestational diabetes are at a higher risk for cesarean delivery and chronic
hypertension. Pregnant patients with T2DM generally have a better prognosis in terms of
neonatal and pregnancy complications compared to those with T1DM. Generally, neonates of
DM mothers will present with hypoglycemia and macrosomia.[52]
The most acute complication of DM is diabetic ketoacidosis (DKA), which typically presents
in T1DM. This condition is usually either due to inadequate dosing, missed doses, or ongoing
infection.[53] In this condition, the lack of insulin means that tissues are unable to obtain
glucose from the bloodstream. Compensation for this causes the metabolism of lipids into
ketones as a substitute energy source, which causes systemic acidosis, and can be calculated
as a high anion-gap metabolic acidosis. The combination of hyperglycemia and ketosis
causes diuresis, acidemia, and vomiting leading to dehydration and electrolyte abnormalities,
which can be lifethreatening.
In T2DM, hyperosmolar hyperglycemic syndrome (HHS) is an emergent concern. It presents
similarly to DKA with excessive thirst, elevated blood glucose, dry mouth, polyuria,
tachypnea, and tachycardia. However, unlike DKA, HHS typically does not present with
excessive urinary ketones since insulin still gets produced by pancreatic beta cells. Treatment
for DKA or HHS involves insulin administration and aggressive intravenous hydration.
Careful management of electrolytes, particularly potassium, is critical in the management of
these emergent conditions.[54]
 CASE STUDY

Case Presentation

A 54 year old female, house wife visited Services Hospital Gurgaon with thecomplaints of
excessive urination, sudden weight loss, blurred vision, increased thirst, fatigue and excessive
sweating. She was experiencing these conditions from last one month. Past Medical History
Patient was also suffering from Hypertension from last 3 years. Past Medication History She
was using Tenormin (Atenolol) 50mg OD from last 3 year

General Examination

Weight: 70kg
Height: 5 foot 2 inches
BMI: 32.01kg/m2
Physical activity: daily work routine home

Special Investigation

According to the reported symptoms, patient’s blood glucose level was monitored. At that
time patient’s random blood glucose level was 196mg/dl which was beyond the normal range
of the random blood glucose level (>140mg/dl). Patient was also said to monitor her fasting
glucose level that was 134mg/dl which was also beyond the normal range (70-100mg/dl).

Treatment

Neodipar-250mg BD (Neodipar is brand and its salt is Metformin HCL)

Interventions

Drug should be taken about 5 -10 minutes before the [Link] of eating a lot at 3 meals,
divide total intake in 5 [Link] interaction was checked, no interaction was present b/w
Atenolol and Metformin. Suggest patient to check HbA1C Level after about every 3rd month
Care Plan

Proper diet ---low sugar intake

Exercise and walk to reduce body weight
High fiber diet less intake of fats and carbohydrates

Outcome

Patient used the suggested medicine Neodipar twice a day after using medicine the blood
glucose level of the patient was monitored.
Fasting = 104mg/dl
After meal = 140mg/dl
Patient was advised to visit hospital if she suffers any side effect in future or, if her symptoms
not properly treated.

Discussion

Patient suffering from diabetes due to many reasons, included less production ofthe insulin by
beta cells of the Pancreas or resistance of body against insulin, a major reason of diabetes is
genetics, majority of diabetic patient suffering from type 2 diabetes due to their genetics and
family history. If this condition is not properly treated or is for long term it results in
cardiovascular disease, shock, permanent damage to eye and chronic kidney disease.

Diabetic patient should properly manage his/her daily dietary intake because if patient is
taking oral hypoglycemic agents as medication and not taking diet according to body need
then he/she may suffer from hypoglycemic state that can be more dangerous than the
hyperglycemia. Small meals should be taken 4 to 5 time in a day instead of eating a lot at
single time.

Insulin or other hypoglycemic agents should always be taken before 10 minutes of taking
meal, because medicine or external source of insulin will trigger the beta cells of the body to
produce insulin inside the body according to need of body. Diabetic condition can also be
treated by non - pharmacological method as by doing exercise, by stopping intake of high
sugar content food.
 CONCLUSION

Diabetes is a slow killer with no known curable treatments. However, itscomplications can be
reduced through proper awareness and timelytreatment. Three major complications are
related to blindness, kidneydamage and heart attack. It is important to keep the blood glucose
levels of patients under strict control for avoiding the complications. One of the difficulties
with tight control of glucose levels in the blood is that such attempts may lead to
hypoglycemia that creates much severe complications than an increased level of blood
glucose. Researchers now look for alternative methods for diabetes treatment. The goal of
this paper is to give a general idea of the current status of diabetes research. The author
believes that diabetes is one of the highly demanding research topics of the new century and
wants to encourage new researchers to take up the challenges

Diabetes is a serious medical condition that affects millions of people worldwide. It can cause
various health complications and should be treated promptly to prevent long-term damage to
the body. By understanding the types, causes, symptoms, and treatment options for diabetes,
individuals can take steps to manage the condition effectively and lead a healthy life. If
you experience any symptoms of diabetes, it is crucial to seek medical attention immediately
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