Use of the Michigan Neuropathy Screening Instrument as a measure of distal symmetrical peripheral neuropathy in Type 1 diabetes: results from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications

Aims  The Michigan Neuropathy Screening Instrument (MNSI) is used to assess distal symmetrical peripheral neuropathy in diabetes. It includes two separate assessments: a 15‐item self‐administered questionnaire and a lower extremity examination that includes inspection and assessment of vibratory sensation and ankle reflexes. The purpose of this study was to evaluate the performance of the MNSI in detecting distal symmetrical peripheral neuropathy in patients with Type 1 diabetes and to develop new scoring algorithms. Methods  The MNSI was performed by trained personnel at each of the 28 Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications clinical sites. Neurologic examinations and nerve conduction studies were performed during the same year. Confirmed clinical neuropathy was defined by symptoms and signs of distal symmetrical peripheral neuropathy based on the examination of a neurologist and abnormal nerve conduction findings in ≥ 2 anatomically distinct nerves among the sural, peroneal and median nerves. Results  We studied 1184 subjects with Type 1 diabetes. Mean age was 47 years and duration of diabetes was 26 years. Thirty per cent of participants had confirmed clinical neuropathy, 18% had ≥ 4 and 5% had ≥ 7 abnormal responses on the MNSI questionnaire, and 33% had abnormal scores (≥ 2.5) on the MNSI examination. New scoring algorithms were developed and cut points defined to improve the performance of the MNSI questionnaire, examination and the combination of the two. Conclusions  Altering the cut point to define an abnormal test from ≥ 7 abnormal to ≥ 4 abnormal items improves the performance of the MNSI questionnaire. The MNSI is a simple, non‐invasive and valid measure of distal symmetrical peripheral neuropathy in Type 1 diabetes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92152/1/j.1464-5491.2012.03644.x.pd

Predictive Clinical Parameters for the Therapeutic Efficacy of Sitagliptin in Korean Type 2 Diabetes Mellitus

BackgroundSitagliptin is a highly selective dipeptidyl peptide-4 (DPP-4) inhibitor that increases blood levels of active glucagon-like peptide (GLP)-1 and glucose-dependent insulinotrophic polypeptide (GIP), resulting in increased insulin secretion. While studies conducted in other countries have indicated the efficacy and safety of using sitagliptin to treat type 2 diabetes mellitus (T2DM), its predictors of effects to sitagliptin are not well understood. Therefore, we evaluated the predictive clinical parameters for the therapeutic benefits of sitagliptin when added to an ongoing metformin or sulfonylurea therapy in Korean T2DM subjects.MethodsWe obtained data from 251 Korean T2DM subjects who had recently started taking sitagliptin as add-on therapy. Exclusion criteria included any insulin use. Changes in HbA1c (ΔHbA1c) and fasting plasma glucose (ΔFPG) were assessed by comparing baseline levels prior to sitagliptin administration to levels 12 and 24 weeks after treatment. Responders were defined as subjects who experienced decrease from baseline of >10% in ΔHbA1c or >20% in ΔFPG levels at 24 weeks.ResultsWe classified 81% of the subjects (204 out of 251) as responders. The responder group had a lower mean body mass index (23.70±2.40 vs. 26.00±2.26, P≤0.01) and were younger (58.83±11.57 years vs. 62.87±12.09 years, P=0.03) than the non-responder group.ConclusionIn Korean T2DM subjects, sitagliptin responders had lower body mass index and were younger compared to non-responders

Biomarkers of tubulointerstitial damage and function in type 1 diabetes

Objective To evaluate biomarkers of renal tubulointerstitial damage and function in type 1 diabetes with and without diabetic kidney disease. Research design and methods Cross-sectional case-control study of Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study participants. Cases (N=43) had incident persistent estimated glomerular filtration rate (eGFR) \u3c60 mL/min/1.73 m2 with urinary albumin excretion \u3e300 mg/24 hour. Controls (N=43) had persistent eGFR \u3e90 mL/min/1.73 m2 and urinary albumin excretion \u3c30 mg/24 hour. Urinary and plasma biomarkers reflecting tubular injury, inflammation, fibrosis, secretion, and synthetic function were measured from stored specimens collected at the first study visit with reduced eGFR (for case participants) or the corresponding study year (for control participants). Results Mean (SD) age was 51 (9) and 50 (8) years for case and control participants, and mean (SD) duration of diabetes was 30 (6) and 30 (5) years, respectively. Mean (SD) eGFR was 39 (14) and 103 (9) mL/min/1.73 m2 for case and control participants, and mean (SD) albumin excretion rate was 1978 (2914) and 10 (7) mg/day, respectively. Comparing cases with controls, significant differences were observed in each measured biomarker, including urine epidermal growth factor (mean 5.3 vs 21.2 μg/g creatinine for case vs control participants, respectively), urine monocyte chemoattractant protein-1 (596 vs 123 ng/g creatinine), urine galectin-3 (168 vs 52 μg/g creatinine), plasma soluble tubular necrosis factor receptor-1 (3695 vs 1022 pg/mL), plasma galectin-3 (21.3 vs 11.0 ng/mL), urinary clearances of hippurate (70 vs 167 mL/min) and cinnamoylglycine (77 vs 317 mL/min), and plasma arginine-citrulline ratio (5.6 vs 7.7 μg/μg), each P\u3c0.001. Conclusions Marked abnormalities in biomarkers of kidney tubular injury, inflammation, fibrosis, secretion, and synthetic function accompany reduced eGFR and albuminuria in type 1 diabetes. Trial registration number NCT00360893, NCT00360815

HbA_1c variability is associated with increased mortality and earlier hospital admission in people with Type 1 diabetes

Aim: Despite evidence of morbidity, no evidence exists on the relationship between HbA1c variability and mortality in Type 1 diabetes. We performed an observational study to investigate whether the association between HbA1c variability and mortality exists in a population of people with Type 1 diabetes. As a secondary outcome, we compared onset of first hospital admission between groups. Methods: People with Type 1 diabetes were identified for inclusion from the Scottish Care Information – Diabetes data set. This database includes data of all people known to have diabetes who live within Scotland. A survival analysis was carried out over a 47‐month period comparing two groups; group 1 with a HbA1c coefficient of variation (CV) above the median CV value, and group 2 with a CV below the median value. Time to death or first admission was also analysed. A Cox proportional hazard model was used to compare time to death, adjusting for appropriate covariables. Results: Some 6048 individuals with Type 1 diabetes were included in the analysis. Median HbA1c CV was 7.9. The hazard ratio (HR) for mortality for those with an HbA1c CV above the median value is 1.5 over 47 months of follow‐up (P < 0.001). HR for survival to either the first admission to hospital or death for those with an HbA1c CV above the median value was 1.35 (95% confidence interval 1.25–1.45) over 730 days of follow‐up (P < 0.001). Conclusion: Our results show that people with greater HbA1c variability have a higher rate of mortality and earlier hospital admission in Type 1 diabetes

A randomized controlled pilot study of continuous glucose monitoring and flash glucose monitoring in people with Type 1 diabetes and impaired awareness of hypoglycaemia

AIM: Hypoglycaemia in Type 1 diabetes is associated with mortality and morbidity, especially where awareness of hypoglycaemia is impaired. Clinical pathways for access to continuous glucose monitoring (CGM) and flash glucose monitoring technologies are unclear. We assessed the impact of CGM and flash glucose monitoring in a high-risk group of people with Type 1 diabetes. METHODS: A randomized, non-masked parallel group study was undertaken. Adults with Type 1 diabetes using a multiple-dose insulin-injection regimen with a Gold score of ≥ 4 or recent severe hypoglycaemia were recruited. Following 2 weeks of blinded CGM, they were randomly assigned to CGM (Dexcom G5) or flash glucose monitoring (Abbott Freestyle Libre) for 8 weeks. The primary outcome was the difference in time spent in hypoglycaemia (below 3.3 mmol/l) from baseline to endpoint with CGM versus flash glucose monitoring. RESULTS: Some 40 participants were randomized to CGM (n = 20) or flash glucose monitoring (n = 20). The participants (24 men, 16 women) had a median (IQR) age of 49.6 (37.5-63.5) years, duration of diabetes of 30.0 (21.0-36.5) years and HbA1c of 56 (48-63) mmol/mol [7.3 (6.5-7.8)%]. The baseline median percentage time < 3.3 mmol/l was 4.5% in the CGM group and 6.7% in the flash glucose monitoring. At the end-point the percentage time < 3.3 mmol/l was 2.4%, and 6.8% respectively (median between group difference -4.3%, P = 0.006). Time spent in hypoglycaemia at all thresholds, and hypoglycaemia fear, were different between groups, favouring CGM. CONCLUSION: CGM more effectively reduces time spent in hypoglycaemia in people with Type 1 diabetes and impaired awareness of hypoglycaemia compared with flash glucose monitoring. (Clinical Trial Registry No: NCT03028220)

Prevalence of Underweight, Overweight, and Obesity in Children and Adolescents with Type 1 Diabetes: Data From the International SWEET Registry

Objective: To assess the prevalence of underweight (UW), overweight (OW), and obesity in children and adolescents with type 1 diabetes (T1D). Methods: An international cross-sectional study including 23 026 T1D children (2-18 years, duration of diabetes ≥1 year) participating in the SWEET prospective, multicenter diabetes registry. Body mass index SD score (BMI-SDS) was calculated using the World Health Organization BMI charts. Children were categorized as UW (BMI-SDS +2SD). Hierarchic regression models were applied with adjustment for sex, age, and duration of diabetes. Results: The prevalence of UW, OW, and obesity was: 1.4%, 22.3%, and 7.3% in males and 0.6%, 27.2%, and 6.8% in females. Adjusted BMI-SDS was significantly higher in females than in males (mean ± SEM: 0.54 ± 0.05 vs 0.40 ± 0.05, P < 0.0001). In males, BMI-SDS significantly decreased by age (P < 0.0001) in the first three age categories 0.61 ± 0.06 (2 to <10 years), 0.47 ± 0.06 (10 to <13 years), 0.34 ± 0.05 (13 to <16 years). In females, BMI-SDS showed a U-shaped distribution by age (P < 0.0001): 0.54 ± 0.04 (2 to <10 years), 0.39 ± 0.04 (10 to <13 years), 0.55 ± 0.04 (13 to <16 years). BMI-SDS increased by diabetes duration (<2 years: 0.38 ± 0.05, 2 to <5 years: 0.44 ± 0.05, and ≥5 years: 0.50 ± 0.05, P < 0.0001). Treatment modality did not affect BMI-SDS. Adjusted HbA1c was significantly higher in females than in males (8.20% ± 0.10% vs 8.06% ± 0.10%, P < 0.0001). In both genders, the association between HbA1c and BMI-SDS was U-shaped with the highest HbA1c in the UW and obesity groups. Conclusions: The high rate of OW and obesity (31.8%) emphasize the need for developing further strategies to prevent and treat excess fat accumulation in T1D.info:eu-repo/semantics/publishedVersio

Day-to-day fasting self-monitored blood glucose variability is associated with risk of hypoglycaemia in insulin-treated patients with type 1 and type 2 diabetes: a post hoc analysis of the SWITCH trials

AIMS: To investigate the association between day-to-day fasting self-monitored blood glucose (SMBG) variability and risk of hypoglycaemia in type 1 (T1D) and type 2 diabetes (T2D), and compare day-to-day fasting SMBG variability between treatments with insulin degludec (degludec) and insulin glargine 100 units/mL (glargine U100). MATERIALS AND METHODS: Data were retrieved from two double-blind, randomised, treat-to-target, two-period (32 weeks each) crossover trials of degludec versus glargine U100 in T1D (SWITCH 1, n=501) and T2D (SWITCH 2, n=720). Available fasting SMBGs were used to determine the standard deviation (SD) of day-to-day fasting SMBG variability for each patient and treatment combination. The association between day-to-day fasting SMBG variability and overall symptomatic, nocturnal symptomatic and severe hypoglycaemia was analysed for the pooled population using linear regression, and with fasting SMBG variability included as a three-level factor defined by population tertiles. Finally, day-to-day fasting SMBG variability was compared between treatments. RESULTS: Linear regression showed that day-to-day fasting SMBG variability was significantly associated with overall symptomatic, nocturnal symptomatic, and severe hypoglycaemia risk in T1D and T2D (p<0.05). Day-to-day fasting SMBG variability was significantly associated (p<0.01) with all categories of hypoglycaemia risk, except for severe hypoglycaemia in T2D when analysed within tertiles. Degludec was associated with 4% lower day-to-day fasting SMBG variability than glargine U100 in T1D (p=0.0082) and 10% lower in T2D (p<0.0001). CONCLUSIONS: Higher day-to-day fasting SMBG variability is associated with an increased risk of overall symptomatic, nocturnal symptomatic and severe hypoglycaemia. Degludec has significantly lower day-to-day fasting SMBG variability versus glargine U100. This article is protected by copyright. All rights reserved

Low-carbohydrate diet in type 2 diabetes: stable improvement of bodyweight and glycemic control during 44 months follow-up

<p>Abstract</p> <p>Background</p> <p>Low-carbohydrate diets, due to their potent antihyperglycemic effect, are an intuitively attractive approach to the management of obese patients with type 2 diabetes. We previously reported that a 20% carbohydrate diet was significantly superior to a 55–60% carbohydrate diet with regard to bodyweight and glycemic control in 2 groups of obese diabetes patients observed closely over 6 months (intervention group, n = 16; controls, n = 15) and we reported maintenance of these gains after 22 months. The present study documents the degree to which these changes were preserved in the low-carbohydrate group after 44 months observation time, without close follow-up. In addition, we assessed the performance of the two thirds of control patients from the high-carbohydrate diet group that had changed to a low-carbohydrate diet after the initial 6 month observation period. We report cardiovascular outcome for the low-carbohydrate group as well as the control patients who did not change to a low-carbohydrate diet.</p> <p>Method</p> <p>Retrospective follow-up of previously studied subjects on a low carbohydrate diet.</p> <p>Results</p> <p>The mean bodyweight at the start of the initial study was 100.6 ± 14.7 kg. At six months it was 89.2 ± 14.3 kg. From 6 to 22 months, mean bodyweight had increased by 2.7 ± 4.2 kg to an average of 92.0 ± 14.0 kg. At 44 months average weight has increased from baseline g to 93.1 ± 14.5 kg. Of the sixteen patients, five have retained or reduced bodyweight since the 22 month point and all but one have lower weight at 44 months than at start. The initial mean HbA1c was 8.0 ± 1.5%. After 6, 12 and 22 months, HbA1c was 6.1 ± 1.0%, 7.0 ± 1.3% and 6.9 ± 1.1% respectively. After 44 months mean HbA1c is 6.8 ± 1.3%.</p> <p>Of the 23 patients who have used a low-carbohydrate diet and for whom we have long-term data, two have suffered a cardiovascular event while four of the six controls who never changed diet have suffered several cardiovascular events.</p> <p>Conclusion</p> <p>Advice to obese patients with type 2 diabetes to follow a 20% carbohydrate diet with some caloric restriction has lasting effects on bodyweight and glycemic control.</p