Background and Aims: It is well-known that diabetes self-management is important for glycemic out... more Background and Aims: It is well-known that diabetes self-management is important for glycemic outcome, also among insulin pump users. We aimed to explore which factors were independently associated with HbA1c. Methods: Adult insulin pump users (18+) with type 1 diabetes from the Capital Region of Denmark completed an online questionnaire covering aspects of insulin pump self-management. HbA1c and demographics were collected from medical records and national registries. Backward selected linear regression models were used to investigate associations between HbA1c and each aspect of self-management, adjusted for one another, CGM/isCGM, sex, age, marital status and educational level. Results: In total, 770 individuals responded; 60% were female, median age was 49 (p25-p75: 36-60) and ranged from 18-86 years, median HbA1c was 56mmol/mol (p25-p75: 50-62) and ranged from 25-135, and 93% used bolus calculator for meal bolus and/or correction. Self-adjustment of pump settings showed the str...
We investigated whether the glomerular synthesis of prostaglandins modulates the glomerular filtr... more We investigated whether the glomerular synthesis of prostaglandins modulates the glomerular filtration rate and albuminuria in diabetic nephropathy. The urinary excretion of immunoreactive prostaglandin E2 (253 pg/min) was significantly elevated in eight Type I (insulin-dependent) diabetic women with nephropathy as compared with nine normoalbuminuric Type 1 diabetic women (95 pg/min) and 11 non-diabetic women (132 pg/min), respectively (p < 0.01). Glomerular filtration rate (single bolus 51Cr-EDTA technique) and albuminuria (radioimmunoassay) were measured twice within two weeks in the eight Type 1 diabetic women with nephropathy. All eight patients were on a diabetic diet without sodium restriction. The study was performed as a randomized doubleblind trial, with the patients receiving either indomethacin (150 mg/day) or placebo for three days prior to the kidney function studies. Indomethacin treatment induced a significant reduction in urinary prostaglandinE2 excretion (73%, p <0.01), glomerular filtration rate diminished from 120 + 18 to 106___ 17 ml/min/1.73 m 2 (p < 0.05), albuminuria declined from 148 to 69 ~tg/min (median and range) (p < 0.05) and fractional clearance of albumin diminished 42% (p < 0.05). Blood glucose concentrations were comparable during the placebo and indomethacin treatment, 13.4 + 4 versus 14.2 + 3 mmol/1, respectively. Our results suggest that glomerular filtration rate in early diabetic nephropathy is dependent on the enhanced glomerular synthesis of vasodilating prostaglandins.
We aimed to evaluate the glycemic effect and detect any predictors of improved time-in-range (TIR... more We aimed to evaluate the glycemic effect and detect any predictors of improved time-in-range (TIR) in persons with type 1 diabetes after initiating hybrid closed-loop (HCL) treatment with MiniMed 670G in a 12-month retrospective observational study. Before starting HCL-treatment, the 62 participants followed a Steno-developed training program; 7 participants (6.5%) discontinued the HCL-therapy; the remaining 55 (58% female) had an age (mean±SD) of 45.6±12.6 years and diabetes duration of 28.2±10.9 years. After 12 months' HCL-therapy, HbA1c decreased from 7.4+0.7% to 7.1+0.5%, TIR increased from 59.3±13.5% to 72±9.3%, time in 54-70 mg/dL (3.0-3.9 mmol/L) decreased from 2.4±2.0% to 1.4±1.0%, and time in 180-250 mg/dL (10.0-13.9 mmol/L) decreased from 26.4±8.3% to 20.8±5.5%, all p<0.001. Improvement in TIR was significantly associated with lower total daily insulin dose, higher amount of total carbohydrate, and more time spent in Auto Mode. Our findings support the promising results on glycemic outcomes seen with HCL treatment.
Diabetic medicine : a journal of the British Diabetic Association, 2014
ABSTRACT Individuals with diabetes struggle with depression, anxiety, distress and other psycholo... more ABSTRACT Individuals with diabetes struggle with depression, anxiety, distress and other psychological problems more often and to a greater degree than do those without a chronic illness. In addition, there is an association between psychological problems and poor diabetes outcomes, such as risk of hyperglycaemia and frequent omission of prescribed medication [1,2]. Unaddressed psychological problems among people with diabetes may therefore have serious clinical consequences. Nevertheless, healthcare professionals do not identify psychological problems in two out of three patients with diabetes [3,4].This article is protected by copyright. All rights reserved.
The purpose of our prospective study was to evaluate the long-term effect of aggressive antihyper... more The purpose of our prospective study was to evaluate the long-term effect of aggressive antihypertensive treatment on glomerular filtration rate and albuminuria in young female and male patients with insulin-dependent diabetes mellitus with diabetic nephropathy and blood pressure greater than 90 mm Hg. Eight patients received treatment with metoprolol (200-400 mg/day), hydralazine (100-200 mg/day), and furosemide (80-500 mg/day). The untreated control group consisted of eight patients matched for age (mean 32 years), diabetes duration (mean 17 years), and sex (two female and six male patients). All patients except one had diabetic retinopathy. Glomerular filtration rate was measured after a single intravenous injection of 51Cr-labeled ethylenediaminetetraacetic acid. Urinary albumin concentration was determined with a radial immunodiffusion method. The investigations were performed two to four times per year in each patient. The mean observation period was 59 and 27 months in the tr...
We investigated the effects of 3 days treatment with acetazolamide 250 mg three times daily on ki... more We investigated the effects of 3 days treatment with acetazolamide 250 mg three times daily on kidney function in 8 Type 1 (insulin-dependent) diabetic patients with nephropathy, and in 7 healthy subjects in a doubleblind placebo controlled cross-over study. Glomerular filtration rate and extracellular fluid volume were measured with the single injection 5tCr-EDTA technique and fluid flow rate from the proximal tubules was determined by measurement of the renal lithium clearance. A 24% decline in glomerular filtration rate was observed in both groups during acetazolamide treatment (control subjects: 108 + 11 vs 82 + 9 ml/min, p<0.02, diabetic patients: 71-+19 vs 54+14ml/min, p <0.01). The renal lithium clearance (ml/min) remained about the same (control subjects: 22-+ 6 vs 27 + 8, NS, diabetic patients: 14_+ 5 vs 15 + 4, NS). Absolute proximal tubular reabsorption of water (ml/min) was reduced by about one-third (control subjects: 85+11 vs 56-+7, p<0.02, diabetic patients: 55 + 17 vs 37+ 6, p < 0.02), and fractional proximal reabsorption of water and sodium (%) declined (control subjects: 79 + 5 vs 67_+ 8, p <0.02, diabetic patients: 79 + 5 vs 72_+ 6, p < 0.02). Renal sodium clearance and distal fractional reabsorption of sodium was unclmnged. Extracellular fluid volume declined by 10% in both groups (p<0.02). Albuminuria and fractional albumin clearance decreased significantly in the nephropathic patients (p < 0.02). Our study suggests that the effects of acetazolamide on kidney function are similar in healthy subjects and patients with diabetic nephropathy.
The effects of strict metabolic control (multiple insulin injections for 1 week) on urinary album... more The effects of strict metabolic control (multiple insulin injections for 1 week) on urinary albumin excretion, glomerular filtration rate and extracellular fluid volume was evaluated in long-term Type 1 diabetic patients with (n = 9) and without (n = 10) incipient nephropathy. Investigations were carried out in poor (blood glucose 15 (interquartile range, 13-18) mmol l-1) and good metabolic control (5 (4-8) mmol l-1). In patients with incipient nephropathy glomerular filtration rate was 125 (SD 26) (poor control) vs 125 (20) ml min-1 (good control), urinary albumin excretion 60 (range 37-247) vs 60 (13-359) mg 24 h-1, fractional albumin clearance 6.1 (0.9-67.6) vs 6.7 (2.1-65.4) x 10(-6), extracellular fluid volume 13.4 (2.3) vs 14.3 (2.8) l (p less than 0.10). Apart from an increase in extracellular fluid volume during improved metabolic control (12.2 (1.6) vs 13.6 (2.5) l, p less than 0.02) all the above mentioned variables remained unchanged in the patients with normal urinary albumin excretion. In conclusion, strict metabolic control for 2-7 days has no effect on urinary albumin excretion and glomerular filtration rate in long-term Type 1 diabetic patients with or without incipient diabetic nephropathy.
The influence of angiotensin II on kidney function in diabetic nephropathy was assessed by studyi... more The influence of angiotensin II on kidney function in diabetic nephropathy was assessed by studying the effect of 12 weeks' monotherapy with captopril (25-50 mg twice a day) in 16 hypertensive insulin dependent diabetic patients with persistent albuminuria. In an initial one week randomised single blind trial of captopril versus placebo, captopril (for nine patients) reduced arterial blood pressure from 148/94 (SD11/6) to 135/88 (8/7) mm Hg (p<005) and albuminuria from 1549 (range 352-2238) to 1170 (297-2198) [ig/min (p<005), while glomerular filtration rate remained stable. No significant changes occurred in seven patients treated with placebo. During the 12 weeks of captopril treatment arterial blood pressure in all patients fell from 147/94 (11/6) to 135/86 (13/7) mm Hg (p<0-01), albuminuria fell from 1589 (range 168-2588) to 1075 (35-2647) Ftg/min (p<0-01), and glomerularfiltration rate fell from 99 (SD19) to 93 (25) ml/min/173 m2 (p<001). The renin-angiotensin system showed suppressed plasma concentrations of angiotensin II and increased concentrations of angiotensin I and renin. The study showed that glomerular filtration rate is not dependent on angiotensin II, that captopril reduces albuminuria, probably by lowering glomerular hypertension, and that captopril represents a valuable new drug for treating hypertension in diabetics dependent on insulin with nephropathy.
The effect of long term, aggressive antihypertensive treatment on kidney function in diabetic nep... more The effect of long term, aggressive antihypertensive treatment on kidney function in diabetic nephropathy was studied prospectively in 11 insulin dependent diabetics (mean age 30). During the mean pretreatment period of 32 (range 23-66) months the glomerular filtration rate decreased significantly and albuminuria and the arterial blood pressure increased significantly. During the 72 (range 32-91) month period of antihypertensive treatment the average arterial blood pressure fell from 143/96 mmHg to 129/84 mm Hg and albuminuria decreased from 1038 [tg/min to 504 [tg/min. The rate of decline in the glomerular filtration rate decreased from 0-89 (range 0.44-1.46) ml/min/month before treatment to 0-22 (range 0-01-0.40) mllmin/month during treatment. The rate of decline in the glomerular filtration rate was significantly smaller during the second three years compared with the first three years in patients who received long term antihypertensive treatment (-6 years). One patient died from acute myocardial infarction (glomerular filtration rate 46 ml/min/ 1-74 m2). Effective antihypertensive treatment postpones renal insufficiency in diabetic nephropathy.
On page 118, third paragraph, line one: the first`14' should be deleted and the sentence should r... more On page 118, third paragraph, line one: the first`14' should be deleted and the sentence should read: ªOf patients with normal UAER (n = 251) 14 died compared with 27 patients with increased UAER (n = 179; p < 0.001).º
Introduction: Insulin pump therapy can improve quality of life and glycaemic outcomes for many pe... more Introduction: Insulin pump therapy can improve quality of life and glycaemic outcomes for many people with type 1 diabetes (T1D). The multidimensional Steno Tech Survey study aims to investigate why some insulin pump users do not achieve treatment goals. In this article, we present the study design and analyse differences in population characteristics between responders and non-responders. Methods: In June 2020, all 1591 insulin pump users (C 18 years) in the Capital Region of Denmark were invited to participate in an online questionnaire that evaluated several dimensions of insulin pump self-management and psychosocial health. Demographic, Karen Rytter and Kristoffer P. Madsen have contributed equally to this work and are considered co-first authors.
Aims/hypothesis The aim of this multicentre, randomised, controlled crossover study was to determ... more Aims/hypothesis The aim of this multicentre, randomised, controlled crossover study was to determine the efficacy of adding continuous glucose monitoring (CGM) to insulin pump therapy (CSII) in type 1 diabetes. Methods Children and adults (n0153) on CSII with HbA 1c 7.5-9.5% (58.5-80.3 mmol/mol) were randomised to (CGM) a Sensor On or Sensor Off arm for 6 months. After 4 months' washout, participants crossed over to the other arm for 6 months. Paediatric and adult participants were separately electronically randomised through the case report form according to a predefined randomisation sequence in eight secondary and tertiary centres. The primary outcome was the difference in HbA 1c levels between arms after 6 months. Results Seventy-seven participants were randomised to the On/Off sequence and 76 to the Off/On sequence; all were included in the primary analysis. The mean difference in HbA 1c was-0.43% (-4.74 mmol/mol) in favour of the Sensor On arm (8.04% [64.34 mmol/mol] vs 8.47% [69.08 mmol/mol]; 95% CI −0.32%, −0.55% [−3.50, −6.01 mmol/mol]; p<0.001). Following cessation of glucose sensing, HbA 1c reverted to baseline levels. Less time was spent with sensor glucose <3.9 mmol/l during the Sensor On arm than in the Sensor Off arm (19 vs 31 min/day; p00.009). The mean number of daily boluses increased in the Sensor On arm (6.8±2.5 vs 5.8±1.9, p<0.0001), together with the frequency of use of the temporary basal rate (0.75± 1.11 vs 0.26±0.47, p<0.0001) and manual insulin suspend (0.91±1.25 vs 0.70±0.75, p<0.018) functions. Four vs two events of severe hypoglycaemia occurred in the Sensor On and Sensor Off arm, respectively (p00.40). Conclusions/interpretation Continuous glucose monitoring was associated with decreased HbA 1c levels and time spent in hypoglycaemia in individuals with type 1 diabetes using CSII. More frequent self-adjustments of insulin therapy may have contributed to these effects.
Aims: We evaluated the urinary orosomucoid excretion (UOE) as a biomarker of preeclampsia and pre... more Aims: We evaluated the urinary orosomucoid excretion (UOE) as a biomarker of preeclampsia and preterm delivery in pregnant women with type 1 diabetes. Methods: Singleton pregnant women with pregestational type 1 diabetes were included provided one urine sample had been collected before 17 gestational weeks. Serum and urinary orosomucoid were analysed by immunoturbidimetry. Primary outcome measurements were development of preeclampsia (blood pressure > 140/90 mmHg and proteinuria) and preterm delivery before 37 weeks. Results: In total 173 women were included. The UOE increased during pregnancy. Preeclampsia developed in 20 women and 65 women delivered preterm. Using logistic regression analysis we found that UOE > 1.37 mg/l (OR: 6.85 (95% CI: 1.97-23.88; p < 0.003)), nulliparity (3.88 (1.10-13.72); p < 0.04), systolic blood pressure > 120 mmHg (4.12 (1.35-12.59); p < 0.02) and duration of diabetes > 20 years (3.69 (1.18-11.52); p < 0.03) independently predicted the development of preeclampsia. Independent predictors of preterm delivery were duration of diabetes and HbA1c > 7%. The remaining covariates included in the regression models were BMI, serum creatinine, smoking and microalbuminuria. Conclusions: Increased UOE early in pregnancy predicted preeclampsia in women with pregestational type 1 diabetes independently of albuminuria and other known risk factors. No association to preterm delivery was found.
Background: Glycemic variability (GV) may attribute to the pathogenesis of diabetic neuropathy. T... more Background: Glycemic variability (GV) may attribute to the pathogenesis of diabetic neuropathy. The aim of this cross-sectional study was to investigate the association between GV and distal symmetric polyneuropathy (DSPN) and cardiovascular autonomic neuropathy (CAN) in a Danish population of young adults with type 1 diabetes. Methods: Young adults between 18 and 24 years with type 1 diabetes were included in this cross-sectional study. CAN was assessed by cardiovascular autonomic reflex tests (CARTs) and heart rate variability (HRV). DSPN was assessed by light pressure, pain and vibration perception, electrochemical skin conductance, sural nerve conduction velocity (SNCV), and amplitude potential (SNAP). GV were obtained by continuous glucose monitoring including coefficient of variation (CV), SD, continuous overall net glycemic action (CONGA), and mean amplitude of glucose excursions (MAGE). Results: The study comprised 133 young adults (43.6% males), mean age of 22 years (SD 1.6). Unadjusted, higher CV was associated with a decreased risk of sural nerve conduction (P = 0.03), abnormal SNAP (P = 0.04) and incidents of definite CAN (P = 0.04). Likewise, higher CONGA was associated with increasing incidents of subclinical DSPN (P = 0.03), abnormal SNAP (P = 0.01), and SNCV (P = 0.02). However, both associations were not statistically significant in the fully adjusted model. Higher MAGE was associated with slightly increasing measures of HRV (P = 0.03) but only when fully adjusted. When correcting for multiple tests significance was lost. A significant association was found between HbA1c and measures of both DSPN (P < 0.02) and HRV (P < 0.03) in fully adjusted models. Conclusions: No significant associations between GV and diabetic neuropathy were found after adjusting for risk factors and multiple tests. This suggests that GV may not be a risk factor for diabetic neuropathy in young adults with type 1 diabetes. However, long-term effects of GV excursions may still play a role in the pathogenic mechanisms leading to neuropathy in later life.
BACKGROUND Carbohydrate counting and use of automated bolus calculators (ABCs) can help reduce Hb... more BACKGROUND Carbohydrate counting and use of automated bolus calculators (ABCs) can help reduce HbA1c in type 1 diabetes but only limited evidence exists in type 2 diabetes. We evaluated the efficacy of advanced carbohydrate counting (ACC) and use of an ABC compared with manual insulin bolus calculation (MC) in persons with type 2 diabetes. MATERIALS AND METHODS A 24-week open-label, randomised clinical study was conducted in 79 persons with type 2 diabetes treated with basal-bolus insulin (mean age 62.5±9.6 years, HbA1c 8.7±1.0% (72±11 mmol/mol), diabetes duration 18.7±7.6 years). Participants were randomised 1:1 into two groups: ABC group received training in ACC and use of an ABC; MC group received training in ACC and manual calculation of insulin bolus. Participants wore blinded continuous glucose monitors (CGM) for six days at baseline and at study end. Primary endpoint was change in HbA1c. RESULTS After 24 weeks HbA1c decreased 0.8% (8.8 mmol/mol) in ABC group and 0.8% (9.0 mmol/mol) in MC group with no between-group difference (P=0.96) and without increase in time in hypoglycaemic range (Sensor glucose (SG)<3.9 mmol/L). Glycaemic variability decreased significantly in both groups whereas the total insulin dose and BMI remained unchanged during the study. Treatment satisfaction increased significantly in both groups after 24 weeks. CONCLUSION ACC is an effective, low-cost tool to reduce HbA1c and glycaemic variability in persons with basal-bolus insulin treated type 2 diabetes without increase in hypoglycaemia or BMI. Similar effects were seen with use of an ABC and with use of manual bolus calculation.
Potential positive impact of group-based diabetes dialogue meetings on diabetes distress and gluc... more Potential positive impact of group-based diabetes dialogue meetings on diabetes distress and glucose control in people with type 1 diabetes. Patient Education and Counseling.
Background and Aims: It is well-known that diabetes self-management is important for glycemic out... more Background and Aims: It is well-known that diabetes self-management is important for glycemic outcome, also among insulin pump users. We aimed to explore which factors were independently associated with HbA1c. Methods: Adult insulin pump users (18+) with type 1 diabetes from the Capital Region of Denmark completed an online questionnaire covering aspects of insulin pump self-management. HbA1c and demographics were collected from medical records and national registries. Backward selected linear regression models were used to investigate associations between HbA1c and each aspect of self-management, adjusted for one another, CGM/isCGM, sex, age, marital status and educational level. Results: In total, 770 individuals responded; 60% were female, median age was 49 (p25-p75: 36-60) and ranged from 18-86 years, median HbA1c was 56mmol/mol (p25-p75: 50-62) and ranged from 25-135, and 93% used bolus calculator for meal bolus and/or correction. Self-adjustment of pump settings showed the str...
We investigated whether the glomerular synthesis of prostaglandins modulates the glomerular filtr... more We investigated whether the glomerular synthesis of prostaglandins modulates the glomerular filtration rate and albuminuria in diabetic nephropathy. The urinary excretion of immunoreactive prostaglandin E2 (253 pg/min) was significantly elevated in eight Type I (insulin-dependent) diabetic women with nephropathy as compared with nine normoalbuminuric Type 1 diabetic women (95 pg/min) and 11 non-diabetic women (132 pg/min), respectively (p < 0.01). Glomerular filtration rate (single bolus 51Cr-EDTA technique) and albuminuria (radioimmunoassay) were measured twice within two weeks in the eight Type 1 diabetic women with nephropathy. All eight patients were on a diabetic diet without sodium restriction. The study was performed as a randomized doubleblind trial, with the patients receiving either indomethacin (150 mg/day) or placebo for three days prior to the kidney function studies. Indomethacin treatment induced a significant reduction in urinary prostaglandinE2 excretion (73%, p <0.01), glomerular filtration rate diminished from 120 + 18 to 106___ 17 ml/min/1.73 m 2 (p < 0.05), albuminuria declined from 148 to 69 ~tg/min (median and range) (p < 0.05) and fractional clearance of albumin diminished 42% (p < 0.05). Blood glucose concentrations were comparable during the placebo and indomethacin treatment, 13.4 + 4 versus 14.2 + 3 mmol/1, respectively. Our results suggest that glomerular filtration rate in early diabetic nephropathy is dependent on the enhanced glomerular synthesis of vasodilating prostaglandins.
We aimed to evaluate the glycemic effect and detect any predictors of improved time-in-range (TIR... more We aimed to evaluate the glycemic effect and detect any predictors of improved time-in-range (TIR) in persons with type 1 diabetes after initiating hybrid closed-loop (HCL) treatment with MiniMed 670G in a 12-month retrospective observational study. Before starting HCL-treatment, the 62 participants followed a Steno-developed training program; 7 participants (6.5%) discontinued the HCL-therapy; the remaining 55 (58% female) had an age (mean±SD) of 45.6±12.6 years and diabetes duration of 28.2±10.9 years. After 12 months' HCL-therapy, HbA1c decreased from 7.4+0.7% to 7.1+0.5%, TIR increased from 59.3±13.5% to 72±9.3%, time in 54-70 mg/dL (3.0-3.9 mmol/L) decreased from 2.4±2.0% to 1.4±1.0%, and time in 180-250 mg/dL (10.0-13.9 mmol/L) decreased from 26.4±8.3% to 20.8±5.5%, all p<0.001. Improvement in TIR was significantly associated with lower total daily insulin dose, higher amount of total carbohydrate, and more time spent in Auto Mode. Our findings support the promising results on glycemic outcomes seen with HCL treatment.
Diabetic medicine : a journal of the British Diabetic Association, 2014
ABSTRACT Individuals with diabetes struggle with depression, anxiety, distress and other psycholo... more ABSTRACT Individuals with diabetes struggle with depression, anxiety, distress and other psychological problems more often and to a greater degree than do those without a chronic illness. In addition, there is an association between psychological problems and poor diabetes outcomes, such as risk of hyperglycaemia and frequent omission of prescribed medication [1,2]. Unaddressed psychological problems among people with diabetes may therefore have serious clinical consequences. Nevertheless, healthcare professionals do not identify psychological problems in two out of three patients with diabetes [3,4].This article is protected by copyright. All rights reserved.
The purpose of our prospective study was to evaluate the long-term effect of aggressive antihyper... more The purpose of our prospective study was to evaluate the long-term effect of aggressive antihypertensive treatment on glomerular filtration rate and albuminuria in young female and male patients with insulin-dependent diabetes mellitus with diabetic nephropathy and blood pressure greater than 90 mm Hg. Eight patients received treatment with metoprolol (200-400 mg/day), hydralazine (100-200 mg/day), and furosemide (80-500 mg/day). The untreated control group consisted of eight patients matched for age (mean 32 years), diabetes duration (mean 17 years), and sex (two female and six male patients). All patients except one had diabetic retinopathy. Glomerular filtration rate was measured after a single intravenous injection of 51Cr-labeled ethylenediaminetetraacetic acid. Urinary albumin concentration was determined with a radial immunodiffusion method. The investigations were performed two to four times per year in each patient. The mean observation period was 59 and 27 months in the tr...
We investigated the effects of 3 days treatment with acetazolamide 250 mg three times daily on ki... more We investigated the effects of 3 days treatment with acetazolamide 250 mg three times daily on kidney function in 8 Type 1 (insulin-dependent) diabetic patients with nephropathy, and in 7 healthy subjects in a doubleblind placebo controlled cross-over study. Glomerular filtration rate and extracellular fluid volume were measured with the single injection 5tCr-EDTA technique and fluid flow rate from the proximal tubules was determined by measurement of the renal lithium clearance. A 24% decline in glomerular filtration rate was observed in both groups during acetazolamide treatment (control subjects: 108 + 11 vs 82 + 9 ml/min, p<0.02, diabetic patients: 71-+19 vs 54+14ml/min, p <0.01). The renal lithium clearance (ml/min) remained about the same (control subjects: 22-+ 6 vs 27 + 8, NS, diabetic patients: 14_+ 5 vs 15 + 4, NS). Absolute proximal tubular reabsorption of water (ml/min) was reduced by about one-third (control subjects: 85+11 vs 56-+7, p<0.02, diabetic patients: 55 + 17 vs 37+ 6, p < 0.02), and fractional proximal reabsorption of water and sodium (%) declined (control subjects: 79 + 5 vs 67_+ 8, p <0.02, diabetic patients: 79 + 5 vs 72_+ 6, p < 0.02). Renal sodium clearance and distal fractional reabsorption of sodium was unclmnged. Extracellular fluid volume declined by 10% in both groups (p<0.02). Albuminuria and fractional albumin clearance decreased significantly in the nephropathic patients (p < 0.02). Our study suggests that the effects of acetazolamide on kidney function are similar in healthy subjects and patients with diabetic nephropathy.
The effects of strict metabolic control (multiple insulin injections for 1 week) on urinary album... more The effects of strict metabolic control (multiple insulin injections for 1 week) on urinary albumin excretion, glomerular filtration rate and extracellular fluid volume was evaluated in long-term Type 1 diabetic patients with (n = 9) and without (n = 10) incipient nephropathy. Investigations were carried out in poor (blood glucose 15 (interquartile range, 13-18) mmol l-1) and good metabolic control (5 (4-8) mmol l-1). In patients with incipient nephropathy glomerular filtration rate was 125 (SD 26) (poor control) vs 125 (20) ml min-1 (good control), urinary albumin excretion 60 (range 37-247) vs 60 (13-359) mg 24 h-1, fractional albumin clearance 6.1 (0.9-67.6) vs 6.7 (2.1-65.4) x 10(-6), extracellular fluid volume 13.4 (2.3) vs 14.3 (2.8) l (p less than 0.10). Apart from an increase in extracellular fluid volume during improved metabolic control (12.2 (1.6) vs 13.6 (2.5) l, p less than 0.02) all the above mentioned variables remained unchanged in the patients with normal urinary albumin excretion. In conclusion, strict metabolic control for 2-7 days has no effect on urinary albumin excretion and glomerular filtration rate in long-term Type 1 diabetic patients with or without incipient diabetic nephropathy.
The influence of angiotensin II on kidney function in diabetic nephropathy was assessed by studyi... more The influence of angiotensin II on kidney function in diabetic nephropathy was assessed by studying the effect of 12 weeks' monotherapy with captopril (25-50 mg twice a day) in 16 hypertensive insulin dependent diabetic patients with persistent albuminuria. In an initial one week randomised single blind trial of captopril versus placebo, captopril (for nine patients) reduced arterial blood pressure from 148/94 (SD11/6) to 135/88 (8/7) mm Hg (p<005) and albuminuria from 1549 (range 352-2238) to 1170 (297-2198) [ig/min (p<005), while glomerular filtration rate remained stable. No significant changes occurred in seven patients treated with placebo. During the 12 weeks of captopril treatment arterial blood pressure in all patients fell from 147/94 (11/6) to 135/86 (13/7) mm Hg (p<0-01), albuminuria fell from 1589 (range 168-2588) to 1075 (35-2647) Ftg/min (p<0-01), and glomerularfiltration rate fell from 99 (SD19) to 93 (25) ml/min/173 m2 (p<001). The renin-angiotensin system showed suppressed plasma concentrations of angiotensin II and increased concentrations of angiotensin I and renin. The study showed that glomerular filtration rate is not dependent on angiotensin II, that captopril reduces albuminuria, probably by lowering glomerular hypertension, and that captopril represents a valuable new drug for treating hypertension in diabetics dependent on insulin with nephropathy.
The effect of long term, aggressive antihypertensive treatment on kidney function in diabetic nep... more The effect of long term, aggressive antihypertensive treatment on kidney function in diabetic nephropathy was studied prospectively in 11 insulin dependent diabetics (mean age 30). During the mean pretreatment period of 32 (range 23-66) months the glomerular filtration rate decreased significantly and albuminuria and the arterial blood pressure increased significantly. During the 72 (range 32-91) month period of antihypertensive treatment the average arterial blood pressure fell from 143/96 mmHg to 129/84 mm Hg and albuminuria decreased from 1038 [tg/min to 504 [tg/min. The rate of decline in the glomerular filtration rate decreased from 0-89 (range 0.44-1.46) ml/min/month before treatment to 0-22 (range 0-01-0.40) mllmin/month during treatment. The rate of decline in the glomerular filtration rate was significantly smaller during the second three years compared with the first three years in patients who received long term antihypertensive treatment (-6 years). One patient died from acute myocardial infarction (glomerular filtration rate 46 ml/min/ 1-74 m2). Effective antihypertensive treatment postpones renal insufficiency in diabetic nephropathy.
On page 118, third paragraph, line one: the first`14' should be deleted and the sentence should r... more On page 118, third paragraph, line one: the first`14' should be deleted and the sentence should read: ªOf patients with normal UAER (n = 251) 14 died compared with 27 patients with increased UAER (n = 179; p < 0.001).º
Introduction: Insulin pump therapy can improve quality of life and glycaemic outcomes for many pe... more Introduction: Insulin pump therapy can improve quality of life and glycaemic outcomes for many people with type 1 diabetes (T1D). The multidimensional Steno Tech Survey study aims to investigate why some insulin pump users do not achieve treatment goals. In this article, we present the study design and analyse differences in population characteristics between responders and non-responders. Methods: In June 2020, all 1591 insulin pump users (C 18 years) in the Capital Region of Denmark were invited to participate in an online questionnaire that evaluated several dimensions of insulin pump self-management and psychosocial health. Demographic, Karen Rytter and Kristoffer P. Madsen have contributed equally to this work and are considered co-first authors.
Aims/hypothesis The aim of this multicentre, randomised, controlled crossover study was to determ... more Aims/hypothesis The aim of this multicentre, randomised, controlled crossover study was to determine the efficacy of adding continuous glucose monitoring (CGM) to insulin pump therapy (CSII) in type 1 diabetes. Methods Children and adults (n0153) on CSII with HbA 1c 7.5-9.5% (58.5-80.3 mmol/mol) were randomised to (CGM) a Sensor On or Sensor Off arm for 6 months. After 4 months' washout, participants crossed over to the other arm for 6 months. Paediatric and adult participants were separately electronically randomised through the case report form according to a predefined randomisation sequence in eight secondary and tertiary centres. The primary outcome was the difference in HbA 1c levels between arms after 6 months. Results Seventy-seven participants were randomised to the On/Off sequence and 76 to the Off/On sequence; all were included in the primary analysis. The mean difference in HbA 1c was-0.43% (-4.74 mmol/mol) in favour of the Sensor On arm (8.04% [64.34 mmol/mol] vs 8.47% [69.08 mmol/mol]; 95% CI −0.32%, −0.55% [−3.50, −6.01 mmol/mol]; p<0.001). Following cessation of glucose sensing, HbA 1c reverted to baseline levels. Less time was spent with sensor glucose <3.9 mmol/l during the Sensor On arm than in the Sensor Off arm (19 vs 31 min/day; p00.009). The mean number of daily boluses increased in the Sensor On arm (6.8±2.5 vs 5.8±1.9, p<0.0001), together with the frequency of use of the temporary basal rate (0.75± 1.11 vs 0.26±0.47, p<0.0001) and manual insulin suspend (0.91±1.25 vs 0.70±0.75, p<0.018) functions. Four vs two events of severe hypoglycaemia occurred in the Sensor On and Sensor Off arm, respectively (p00.40). Conclusions/interpretation Continuous glucose monitoring was associated with decreased HbA 1c levels and time spent in hypoglycaemia in individuals with type 1 diabetes using CSII. More frequent self-adjustments of insulin therapy may have contributed to these effects.
Aims: We evaluated the urinary orosomucoid excretion (UOE) as a biomarker of preeclampsia and pre... more Aims: We evaluated the urinary orosomucoid excretion (UOE) as a biomarker of preeclampsia and preterm delivery in pregnant women with type 1 diabetes. Methods: Singleton pregnant women with pregestational type 1 diabetes were included provided one urine sample had been collected before 17 gestational weeks. Serum and urinary orosomucoid were analysed by immunoturbidimetry. Primary outcome measurements were development of preeclampsia (blood pressure > 140/90 mmHg and proteinuria) and preterm delivery before 37 weeks. Results: In total 173 women were included. The UOE increased during pregnancy. Preeclampsia developed in 20 women and 65 women delivered preterm. Using logistic regression analysis we found that UOE > 1.37 mg/l (OR: 6.85 (95% CI: 1.97-23.88; p < 0.003)), nulliparity (3.88 (1.10-13.72); p < 0.04), systolic blood pressure > 120 mmHg (4.12 (1.35-12.59); p < 0.02) and duration of diabetes > 20 years (3.69 (1.18-11.52); p < 0.03) independently predicted the development of preeclampsia. Independent predictors of preterm delivery were duration of diabetes and HbA1c > 7%. The remaining covariates included in the regression models were BMI, serum creatinine, smoking and microalbuminuria. Conclusions: Increased UOE early in pregnancy predicted preeclampsia in women with pregestational type 1 diabetes independently of albuminuria and other known risk factors. No association to preterm delivery was found.
Background: Glycemic variability (GV) may attribute to the pathogenesis of diabetic neuropathy. T... more Background: Glycemic variability (GV) may attribute to the pathogenesis of diabetic neuropathy. The aim of this cross-sectional study was to investigate the association between GV and distal symmetric polyneuropathy (DSPN) and cardiovascular autonomic neuropathy (CAN) in a Danish population of young adults with type 1 diabetes. Methods: Young adults between 18 and 24 years with type 1 diabetes were included in this cross-sectional study. CAN was assessed by cardiovascular autonomic reflex tests (CARTs) and heart rate variability (HRV). DSPN was assessed by light pressure, pain and vibration perception, electrochemical skin conductance, sural nerve conduction velocity (SNCV), and amplitude potential (SNAP). GV were obtained by continuous glucose monitoring including coefficient of variation (CV), SD, continuous overall net glycemic action (CONGA), and mean amplitude of glucose excursions (MAGE). Results: The study comprised 133 young adults (43.6% males), mean age of 22 years (SD 1.6). Unadjusted, higher CV was associated with a decreased risk of sural nerve conduction (P = 0.03), abnormal SNAP (P = 0.04) and incidents of definite CAN (P = 0.04). Likewise, higher CONGA was associated with increasing incidents of subclinical DSPN (P = 0.03), abnormal SNAP (P = 0.01), and SNCV (P = 0.02). However, both associations were not statistically significant in the fully adjusted model. Higher MAGE was associated with slightly increasing measures of HRV (P = 0.03) but only when fully adjusted. When correcting for multiple tests significance was lost. A significant association was found between HbA1c and measures of both DSPN (P < 0.02) and HRV (P < 0.03) in fully adjusted models. Conclusions: No significant associations between GV and diabetic neuropathy were found after adjusting for risk factors and multiple tests. This suggests that GV may not be a risk factor for diabetic neuropathy in young adults with type 1 diabetes. However, long-term effects of GV excursions may still play a role in the pathogenic mechanisms leading to neuropathy in later life.
BACKGROUND Carbohydrate counting and use of automated bolus calculators (ABCs) can help reduce Hb... more BACKGROUND Carbohydrate counting and use of automated bolus calculators (ABCs) can help reduce HbA1c in type 1 diabetes but only limited evidence exists in type 2 diabetes. We evaluated the efficacy of advanced carbohydrate counting (ACC) and use of an ABC compared with manual insulin bolus calculation (MC) in persons with type 2 diabetes. MATERIALS AND METHODS A 24-week open-label, randomised clinical study was conducted in 79 persons with type 2 diabetes treated with basal-bolus insulin (mean age 62.5±9.6 years, HbA1c 8.7±1.0% (72±11 mmol/mol), diabetes duration 18.7±7.6 years). Participants were randomised 1:1 into two groups: ABC group received training in ACC and use of an ABC; MC group received training in ACC and manual calculation of insulin bolus. Participants wore blinded continuous glucose monitors (CGM) for six days at baseline and at study end. Primary endpoint was change in HbA1c. RESULTS After 24 weeks HbA1c decreased 0.8% (8.8 mmol/mol) in ABC group and 0.8% (9.0 mmol/mol) in MC group with no between-group difference (P=0.96) and without increase in time in hypoglycaemic range (Sensor glucose (SG)<3.9 mmol/L). Glycaemic variability decreased significantly in both groups whereas the total insulin dose and BMI remained unchanged during the study. Treatment satisfaction increased significantly in both groups after 24 weeks. CONCLUSION ACC is an effective, low-cost tool to reduce HbA1c and glycaemic variability in persons with basal-bolus insulin treated type 2 diabetes without increase in hypoglycaemia or BMI. Similar effects were seen with use of an ABC and with use of manual bolus calculation.
Potential positive impact of group-based diabetes dialogue meetings on diabetes distress and gluc... more Potential positive impact of group-based diabetes dialogue meetings on diabetes distress and glucose control in people with type 1 diabetes. Patient Education and Counseling.
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Papers by Eva Hommel