Fasting and meal-stimulated serum C-peptide in long-standing type 1 diabetes mellitus.

AIMS: This study aims to evaluate the stability of C-peptide over time and to compare fasting C-peptide and C-peptide response after mixed-meal tolerance test (MMTT) at T90 or T120 with C-peptide area under the curve (AUC) in long-standing type 1 diabetes. METHODS: We included 607 type 1 diabetes individuals with diabetes duration >5 years. C-peptide concentrations (ultrasensitive assay) were collected in the fasting state, and in a subpopulation after MMTT (T0, just prior to, T30-T60-T90-T120, 30-120 min after ingestion of mixed-meal) (n = 168). Fasting C-peptide concentrations (in n = 535) at Year 0 and Year 1 were compared. The clinical determinants associated with residual C-peptide secretion and the correspondence of C-peptide at MMTT T90 / T120 and total AUC were assessed. RESULTS: A total of 153 participants (25%) had detectable fasting serum C-peptide (i.e ≥ 3.8 pmol/L). Fasting C-peptide was significantly lower at Year 1 (p < 0.001, effect size = -0.16). Participants with higher fasting C-peptide had a higher age at diagnosis and shorter disease duration and were less frequently insulin pump users. Overall, 109 of 168 (65%) participants had both non-detectable fasting and post-meal serum C-peptide concentrations. The T90 and T120 C-peptide values at MMTT were concordant with total AUC. In 17 (10%) individuals, C-peptide was only detectable at MMTT and not in the fasting state. CONCLUSIONS: Stimulated C-peptide was detectable in an additional 10% of individuals compared with fasting in individuals with >5 years of diabetes duration. T90 and T120 MMTT measurements showed good concordance with the MMTT total AUC. Overall, there was a decrease of C-peptide at 1-year follow-up.

Cohort profile: the 'Biomarkers of heterogeneity in type 1 diabetes' study-a national prospective cohort study of clinical and metabolic phenotyping of individuals with long-standing type 1 diabetes in the Netherlands.

PURPOSE: The 'Biomarkers of heterogeneity in type 1 diabetes' study cohort was set up to identify genetic, physiological and psychosocial factors explaining the observed heterogeneity in disease progression and the development of complications in people with long-standing type 1 diabetes (T1D). PARTICIPANTS: Data and samples were collected in two subsets. A prospective cohort of 611 participants aged ≥16 years with ≥5 years T1D duration from four Dutch Diabetes clinics between 2016 and 2021 (median age 32 years; median diabetes duration 12 years; 59% female; mean glycated haemoglobin (HbA1c) 61 mmol/mol (7.7%); 61% on insulin pump; 23% on continuous glucose monitoring (CGM)). Physical assessments were performed, blood and urine samples were collected, and participants completed questionnaires. A subgroup of participants underwent mixed-meal tolerance tests (MMTTs) at baseline (n=169) and at 1-year follow-up (n=104). Genetic data and linkage to medical and administrative records were also available. A second cross-sectional cohort included participants with ≥35 years of T1D duration (currently n=160; median age 64 years; median diabetes duration 45 years; 45% female; mean HbA1c 58 mmol/mol (7.4%); 51% on insulin pump; 83% on CGM), recruited from five centres and measurements, samples and 5-year retrospective data were collected. FINDINGS TO DATE: Stimulated residual C-peptide was detectable in an additional 10% of individuals compared with fasting residual C-peptide secretion. MMTT measurements at 90 min and 120 min showed good concordance with the MMTT total area under the curve. An overall decrease of C-peptide at 1-year follow-up was observed. Fasting residual C-peptide secretion is associated with a decreased risk of impaired awareness of hypoglycaemia. FUTURE PLANS: Research groups are invited to consider the use of these data and the sample collection. Future work will include additional hormones, beta-cell-directed autoimmunity, specific immune markers, microRNAs, metabolomics and gene expression data, combined with glucometrics, anthropometric and clinical data, and additional markers of residual beta-cell function. TRIAL REGISTRATION NUMBER: NCT04977635.

Type 2 diabetes in South Asians compared to Europeans: Higher risk and earlier development of major cardiovascular events irrespective of the presence and degree of retinopathy. Results from The HinDu The Hague Diabetes Study.

INTRODUCTION: South Asians with diabetes have more severe diabetic retinopathy (DR) and cardiovascular complications than white Caucasians. However, how big this gap is and the relation with the severity of DR has not been studied. Here, we quantify the difference in time from diabetes diagnosis until a first non-fatal Major Adverse Cardiovascular Event (TUF MACE) in different DR groups in South Asians and Europeans. METHODS: 3831 adults with type 2 diabetes, 1358 South Asians and 2473 Europeans, treated in our diabetes clinic between 2006 and 2017 were included. Data on risk factors, diabetes duration, age of diagnosis and diabetes complications were collected from the diabetes-specific database and analysed using descriptive statistics and Cox regression. DR was graded in 3 categories, and non-fatal MACE was pre-specified. RESULTS: Prevalence of non-fatal MACE was the same when DR was absent, increased with increasing severity of DR in both ethnic groups, but was more frequent in South Asians with DR (mild: 50 vs. 42% and severe 62 vs. 46%. Classic risk factors only differed in relation to smoking habits, which were significantly lower in South Asians.After correction for classic risk factors and age at diabetes diagnosis TUF MACE was significantly shorter in South Asians, an effect also seen in the no-DR group (4.1 yrs. HR 1.5, 95% CI 1.3-1.8 and 7.4 yrs. earlier, HR 2.0, 95% CI 1.6-2.6 for no-DR and severe DR, respectively). CONCLUSIONS: When adjusted for age at diabetes diagnosis, we show that time until first non-fatal MACE in South Asians is significantly shorter compared to Europeans and increases from no- to severe DR.

Daily oral pamidronate in women and men with osteoporosis: a 3-year randomized placebo-controlled clinical trial with a 2-year open extension.

The efficacy and safety of oral pamidronate was examined in a double-blind, placebo-controlled trial in women and men with established osteoporosis. Seventy-eight postmenopausal women and 23 men with at least one prevalent vertebral fracture were randomized separately to 150 mg/day of pamidronate or placebo for 3 years followed by 150 mg/day of pamidronate for an additional 2 years. In addition, all patients received 400 U/day of cholecalciferol and 500 mg/day of elemental calcium. Pamidronate increased significantly bone mineral density of the lumbar spine (LS-BMD) and of the femoral neck (FN-BMD). The total increase in BMD of the spine after 5 years of treatment was 14.3%. Lateral spine radiographs were obtained at baseline and after 3 years of treatment. Fractures of previously normal vertebrae occurred in 15 of 45 patients treated with placebo (33.3%) and in 5 of 46 patients treated with pamidronate (11%). The relative risk was 0.33 (95% CI, 0.14-0.77). Treatment was well tolerated and there was no difference in gastrointestinal toxicity between pamidronate and placebo-treated patients. One hundred fifty milligrams daily of pamidronate is an effective and safe treatment of women and men with established osteoporosis.

Similar adverse pregnancy outcome in native and nonnative dutch women with pregestational type 2 diabetes: a multicentre retrospective study.

Objective. To assess the incidence of adverse pregnancy outcome in native and nonnative Dutch women with pregestational type 2 diabetes (T2D) in a multicenter study in The Netherlands. Methods. Maternal characteristics and pregnancy outcome were retrospectively reviewed and the influence of ethnicity on outcome was evaluated using independent t-test, Mann-Whitney U-test, and chi-square test. Results. 272 pregnant women (80 native and 192 non-native Dutch) with pregestational T2D were included. Overall outcome was unfavourable, with a perinatal mortality of 4.8%, major congenital malformations of 6.3%, preeclampsia of 11%, preterm birth of 19%, birth weight >90th percentile of 32%, and a Caesarean section rate of 42%. In nonnative Dutch women, the glycemic control was slightly poorer and the gestational age at booking somewhat later as compared to native Dutch women. However, there were no differences in incidence of preeclampsia/HELLP, preterm birth, perinatal mortality, macrosomia, and congenital malformations between those two groups. Conclusions. A high incidence of adverse pregnancy outcomes was found in women with pregestational T2D, although the outcome was comparable between native and non-native Dutch women. This suggests that easy access to and adequate participation in the local health care systems contribute to these comparable outcomes, offsetting potential disadvantages in the non-native group.

Family communication as strategy in diabetes prevention: an observational study in families with Dutch and Surinamese South-Asian ancestry.

OBJECTIVE: To explore the possibility of utilizing family communication as a diabetes prevention strategy, specifically targeting high-risk families with South-Asian ancestry in The Netherlands. METHODS: In a cross-sectional study, type 2 diabetes patients from Dutch (n=311) and Surinamese South-Asian (n=157) origin filled in a questionnaire assessing socio-demographic characteristics, beliefs and concerns about familial diabetes risk, primary prevention, and diabetes-related family communication. RESULTS: Discussing diabetes is regarded acceptable in most families. Especially Surinamese South-Asian patients (68%) seemed motivated to convey risk messages to their relatives; they reported a higher risk perception and expressed more concern than Dutch patients. While 40% in both groups thought relatives are able to prevent developing diabetes, 46% in Dutch and 33% in Surinamese South-Asian patients were unsure. CONCLUSION: Promoting family communication appears a feasible strategy in diabetes prevention in high-risk (Surinamese South-Asian) families. Health care providers should address patients' concern and emphasize opportunities for prevention. PRACTICE IMPLICATIONS: Findings favor training of clinicians in utilizing a family approach as prevention strategy. Patients (particularly Surinamese South-Asians) are in need of professional help in the process of family risk disclosure. (Online) Educational tools should be made available at which patients can refer their relatives.