Dataset Information

Persistent C-peptide is associated with reduced hypoglycaemia but not HbA_1c in adults with longstanding Type 1 diabetes: evidence for lack of intensive treatment in UK clinical practice?

ABSTRACT:

Aims

Most people with Type 1 diabetes have low levels of persistent endogenous insulin production. The Diabetes Control and Complications Trial showed that close to diagnosis preserved endogenous insulin was associated with lower HbA_1c , hypoglycaemia and complication rates, when intensively treated. We aimed to assess the clinical impact of persistent C-peptide on rate of hypoglycaemia and HbA_1c in those with long duration (> 5 years) Type 1 diabetes.

Methods

We conducted a cross-sectional case-control study of 221 people (median age 24 years) with Type 1 diabetes. We confirmed ongoing endogenous insulin secretion by measuring C-peptide after a mixed-meal tolerance test. We compared self-reported hypoglycaemia (n = 160), HbA_1c , insulin dose and microvascular complications (n = 140) in those with preserved and low C-peptide.

Results

Stimulated median (IQR) C-peptide was 114 (43, 273) pmol/l and < 3 (< 3, < 3) pmol/l in those with preserved and low C-peptide respectively. Participants with preserved C-peptide had lower reported monthly rates of hypoglycaemia, with 21% fewer symptomatic episodes, 5.9 vs. 7.5 [incidence rate ratio (IRR) 0.79, P = 0.001], and 65% fewer asymptomatic episodes, 1.0 vs. 2.9 (IRR 0.35, P < 0.001). Those with preserved C-peptide had a lower insulin dose (0.68 vs. 0.81 units/kg, P = 0.01) but similar HbA_1c (preserved 69 vs. low 67 mmol/mol, P = 0.06).

Conclusions

Adults with Type 1 diabetes and preserved endogenous insulin production receiving usual care in the UK have lower daily insulin doses and fewer self-reported hypoglycaemic episodes, but no difference in HbA_1c . This is consistent with non-intensive treatment in previous studies, and suggests a need to consider therapy intensification to gain full benefit of preserved endogenous insulin.

SUBMITTER: Marren SM

PROVIDER: S-EPMC6790586 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Publications

Persistent C-peptide is associated with reduced hypoglycaemia but not HbA<sub>1c</sub> in adults with longstanding Type 1 diabetes: evidence for lack of intensive treatment in UK clinical practice?

Marren S M SM Hammersley S S McDonald T J TJ Shields B M BM Knight B A BA Hill A A Bolt R R Tree T I TI Roep B O BO Hattersley A T AT Jones A G AG Oram R A RA

Diabetic medicine : a journal of the British Diabetic Association 20190627 9

<h4>Aims</h4>Most people with Type 1 diabetes have low levels of persistent endogenous insulin production. The Diabetes Control and Complications Trial showed that close to diagnosis preserved endogenous insulin was associated with lower HbA<sub>1c</sub> , hypoglycaemia and complication rates, when intensively treated. We aimed to assess the clinical impact of persistent C-peptide on rate of hypoglycaemia and HbA<sub>1c</sub> in those with long duration (> 5 years) Type 1 diabetes.<h4>Methods</h ...[more]

PMID: 30955221

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Project description:Aims/hypothesisThe aim of the study was to evaluate longitudinal associations between HbA1c levels, diabetes status and subsequent cognitive decline over a 10 year follow-up period.MethodsData from wave 2 (2004-2005) to wave 7 (2014-2015) of the English Longitudinal Study of Ageing (ELSA) were analysed. Cognitive function was assessed at baseline (wave 2) and reassessed every 2 years at waves 3-7. Linear mixed models were used to evaluate longitudinal associations.ResultsThe study comprised 5189 participants (55.1% women, mean age 65.6 ± 9.4 years) with baseline HbA1c levels ranging from 15.9 to 126.3 mmol/mol (3.6-13.7%). The mean follow-up duration was 8.1 ± 2.8 years and the mean number of cognitive assessments was 4.9 ± 1.5. A 1 mmol/mol increment in HbA1c was significantly associated with an increased rate of decline in global cognitive z scores (-0.0009 SD/year, 95% CI -0.0014, -0.0003), memory z scores (-0.0005 SD/year, 95% CI -0.0009, -0.0001) and executive function z scores (-0.0008 SD/year, 95% CI -0.0013, -0.0004) after adjustment for baseline age, sex, total cholesterol, HDL-cholesterol, triacylglycerol, high-sensitivity C-reactive protein, BMI, education, marital status, depressive symptoms, current smoking, alcohol consumption, hypertension, CHD, stroke, chronic lung disease and cancer. Compared with participants with normoglycaemia, the multivariable-adjusted rate of global cognitive decline associated with prediabetes and diabetes was increased by -0.012 SD/year (95% CI -0.022, -0.002) and -0.031 SD/year (95% CI -0.046, -0.015), respectively (p for trend <0.001). Similarly, memory, executive function and orientation z scores showed an increased rate of cognitive decline with diabetes.Conclusions/interpretationSignificant longitudinal associations between HbA1c levels, diabetes status and long-term cognitive decline were observed in this study. Future studies are required to determine the effects of maintaining optimal glucose control on the rate of cognitive decline in people with diabetes.

Project description:BackgroundCombining HbA1c with glycated albumin (GA) may improve detection of dysglycaemia. As BMI correlates positively with HbA1c and negatively with GA, HbA1c may be more effective in obese and GA in nonobese individuals.MethodsTo relate these findings to Africans, we assessed in 1274 South Africans living in CapeTown (male 26%; age 48±16y; BMI 28.7 kg/m2 (range 15.6-73.8); obesity 39.9% and no prior diabetes history) the: (1) correlation of BMI with HbA1c and GA, (2) ability of HbA1c and GA separately and jointly, to detect OGTT-diagnosed dysglycaemia (diabetes plus prediabetes). Data collection took place between 2014 and 2016 in the City of Cape Town. Dysglycaemia was diagnosed by glucose criteria for the OGTT. Youden index was used to optimize diagnostic thresholds for HbA1c and GA.FindingsNormal glucose tolerance, prediabetes and diabetes occurred in 76%, 17% and 7%, respectively. BMI positively correlated with HbA1c [r = 0·34 [95%CI: 0·29,0·39)] and negatively with GA [-0·08 (0·13,0·03)]. For HbA1c the optimal threshold by Youden-index for dysglycaemia diagnosis was: 6·0% (95%CI: 5·8,6·2) and for GA: 13·44% (12·72,14·71). In the nonobese, obese and total cohort, HbA1c-alone detected: 51% (42-60), 72% (65,78), 63% (57,68), respectively; GA-alone detected 55% (52% (46,63), 52% (44, 59) and 53% (47,53), respectively; whereas: HbA1c+GA detected: 69% (60,76), 82% (75,87) and 76% (71, 81). Therefore, for the total cohort detection of dysglycaemia HbA1c-alone vs HbA1c+GA detected 63% (57,68) vs 76% (71,81).InterpretationThe opposite correlations of HbA1c and GA with BMI have now been demonstrated in an African-based population. Improving detection of dysglycaemia by combining HbA1c and GA has important implications for diabetes risk screening.FundingAES is supported by the intramural programs of the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Minority Health and Health Disparities of the National Institutes of Health (NIH, Bethesda, Maryland, USA). DBS is supported by the intramural program of the Clinical Center of NIH. The South African Medical Research Council (SAMRC) funded the VMH study with funds from the National Treasury under its Economic Competitiveness and Support Package (MRC-RFA-UFSP-01-2013/VMH Study).

Dataset Information

Persistent C-peptide is associated with reduced hypoglycaemia but not HbA_1c in adults with longstanding Type 1 diabetes: evidence for lack of intensive treatment in UK clinical practice?

Aims

Methods

Results

Conclusions

Publications

Persistent C-peptide is associated with reduced hypoglycaemia but not HbA<sub>1c</sub> in adults with longstanding Type 1 diabetes: evidence for lack of intensive treatment in UK clinical practice?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Persistent C-peptide is associated with reduced hypoglycaemia but not HbA1c in adults with longstanding Type 1 diabetes: evidence for lack of intensive treatment in UK clinical practice?

Aims

Methods

Results

Conclusions

Publications

Persistent C-peptide is associated with reduced hypoglycaemia but not HbA<sub>1c</sub> in adults with longstanding Type 1 diabetes: evidence for lack of intensive treatment in UK clinical practice?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Persistent C-peptide is associated with reduced hypoglycaemia but not HbA_1c in adults with longstanding Type 1 diabetes: evidence for lack of intensive treatment in UK clinical practice?