Sex differences in the association between plasma copeptin and incident type 2 diabetes: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study

Aims/hypothesis

Vasopressin plays a role in osmoregulation, glucose homeostasis and inflammation. Therefore, plasma copeptin, the stable C-terminal portion of the precursor of vasopressin, has strong potential as a biomarker for the cardiometabolic syndrome and diabetes. Previous results were contradictory, which may be explained by differences between men and women in responsiveness of the vasopressin system. The aim of this study was to evaluate the usefulness of copeptin for prediction of future type 2 diabetes in men and women separately.

Methods

From the Prevention of Renal and Vascular Endstage Disease (PREVEND) study, 4,063 women and 3,909 men without diabetes at baseline were included. A total of 208 women and 288 men developed diabetes during a median follow-up of 7.7?years.

Results

In multivariable-adjusted models, we observed a stronger association of copeptin with risk of future diabetes in women (OR 1.49 [95% CI 1.24, 1.79]) than in men (OR 1.01 [95% CI 0.85, 1.19]) (p _interaction?p?=?0.02) and reclassification (integrated discrimination improvement [IDI] = 0.004, p?Conclusions/interpretation The association of plasma copeptin with the risk of developing diabetes was stronger in women than in men. Plasma copeptin alone, and along with existing biomarkers (glucose, hs-CRP and UAE), significantly improved the risk prediction for diabetes in women.     

Circulating adiponectin levels and risk of type 2 diabetes in the Japanese

Background:

Adiponectin has anti-inflammatory and insulin-sensitizing properties. Prospective studies have consistently shown a lower risk of type 2 diabetes among those with higher circulating adiponectin levels.

Objective:

We examined prospectively the association between serum adiponectin levels and type 2 diabetes risk among Japanese workers, taking visceral fat mass into account.

Subjects and methods:

Subjects were 4591 Japanese employees who attended a comprehensive health screening in 2008; had biochemical data including serum adiponectin; were free of diabetes at baseline; and received health screening in 2011. Multiple logistic regression analysis was used to examine the association between adiponectin and incidence of diabetes among overall subjects, as well as subgroups. Stratified analyses were carried out according to variables including visceral fat area (VFA).

Results:

During 3 years of follow-up, 217 diabetic cases were newly identified. Of these, 87% had a prediabetes at baseline. Serum adiponectin level was significantly, inversely associated with incidence of diabetes, with odds ratios (95% confidence interval) adjusted for age, sex, family history, smoking, alcohol drinking, physical activity and body mass index (BMI) for the lowest through highest quartile of adiponectin of 1 (reference), 0.79 (0.55–1.12), 0.60 (0.41–0.88) and 0.40 (0.25–0.64), respectively (P-value for trend <0.01). This association was materially unchanged with adjustment for VFA instead of BMI. After further adjustment for both homeostasis model assessment of insulin resistance and hemoglobin A1c, however, the association became statistically nonsignificant (P-value for trend=0.18). Risk reduction associated with higher adiponectin levels was observed in both participants with and without obesity or insulin resistance at baseline.

Conclusions:

Results suggest that higher levels of circulating adiponectin are associated with a lower risk of type 2 diabetes, independently of overall and intra-abdominal fat deposition, and that adiponectin may confer a benefit in both persons with and without insulin resistance.     

Circulating IL-18 and the risk of type 2 diabetes in women

Aims/hypothesis  

The pathophysiology of type 2 diabetes involves pro-inflammatory pathways. We tested the hypothesis that IL-18 predicts future diabetes cases.     

Microalbuminuria is independently associated with ischaemic electrocardiographic abnormalities in a large non-diabetic population. The PREVEND (Prevention of REnal and Vascular ENdstage Disease) study.

AIM: To assess the value of microalbuminuria as an indicator of increased cardiovascular risk in a non-diabetic population. METHODS AND RESULTS: 7579 non-diabetic subjects were studied with ages ranging from 28 to 75 years selected from a population based cohort. Using computerized Minnesota coding, ischaemic electrocardiographic abnormalities were divided into three categories: infarct patterns, major ischaemia, and minor ischaemia. Urinary albumin excretion was measured as the mean of two 24-h urine collections. Cardiovascular risk indicators were defined as an age above 60 years, male sex, hypertension, hypercholesterolaemia, smoking, obesity and a positive cardiovascular family history. Microalbuminuria was associated with age, sex, blood pressure, serum cholesterol, serum glucose, body mass index and all three categories of electrocardiographic abnormalities. In a multivariate model, adjusted for established cardiovascular risk indicators, microalbuminuria was independently associated with infarct patterns (OR [95% CI] 1.61 [1.12-2.32]), major ischaemia (OR 1.43 [1.08-1.91]) and minor ischaemia (OR 1.32 [1.03-1.68]). CONCLUSIONS: The independent association between microalbuminuria and ischaemic electrocardiographic abnormalities suggests that microalbuminuria has additional value to conventional risk indicators in predicting cardiovascular disease in non-diabetics. Assessment of microalbuminuria could be an instrument to identify those at an increased risk for coronary vascular disease in an early stage.     

Circulating prolactin concentrations and risk of type 2 diabetes in US women

Aims/hypothesis

Prolactin, a multifunctional hormone, is involved in regulating insulin sensitivity and glucose homeostasis in experimental studies. However, whether circulating concentrations of prolactin are associated with risk of type 2 diabetes remains uncertain.

Methods

We analysed the prospective relationship between circulating prolactin concentrations and type 2 diabetes risk in the Nurses’ Health Study (NHS) and NHSII with up to 22 years of follow-up. Total plasma prolactin was measured using immunoassay in 8615 women free of type 2 diabetes and cardiovascular disease at baseline blood collection (NHS 1989–1990; NHSII 1996–1999) and a subset of 998 NHS women providing a second blood sample during 2000–2002. Baseline bioactive prolactin was measured in a subset of 2478 women using the Nb2 bioassay. HRs were estimated using Cox regression.

Results

A total of 699 incident type 2 diabetes cases were documented during 156,140 person-years of follow-up. Total plasma prolactin levels were inversely associated with type 2 diabetes risk; the multivariable HR comparing the highest with the lowest quartile was 0.73 (95% CI 0.55, 0.95; p_trend?=?0.02). The associations were similar by menopausal status and other risk factors (p_interaction?>?0.70). Additional adjustment for sex and growth hormones, adiponectin, and inflammatory and insulin markers did not significantly alter the results. The association of plasma bioactive prolactin with type 2 diabetes risk was non-significantly stronger than that of total prolactin (HR comparing extreme quartiles, 0.53 vs 0.81 among the subset of 2478 women, p_difference?=?0.11). The inverse association of total prolactin with type 2 diabetes was significant during the first 9 years after blood draw but waned linearly with time, whereas for bioactive prolactin, the inverse relationship persisted for a longer follow-up time after blood draw.

Conclusions/interpretation

A normally high circulating total prolactin concentration was associated with a lower type 2 diabetes risk within 9–10 years of follow-up since blood draw in US women. Our findings are consistent with experimental evidence, suggesting that among healthy women, prolactin within the biologically normal range may play a protective role in the pathogenesis of type 2 diabetes.

     

Smoking habits and the risk of type 2 diabetes: A case-control study

AimThe objective of the study was to assess the relationship between smoking and the risk of type 2 diabetes.Subject and methodsThis case-control study included 234 cases with newly confirmed diagnoses of type 2 diabetes and 468 controls who were free of the disease in 2001. Cases and controls were matched by gender and age (±5 years). A questionnaire was used to collect information on the possible risk factors of type 2 diabetes. Clinical measurements were taken in accordance with the recommendations of the WHO. Fasting plasma glucose and triglycerides were also measured, and the glucose tolerance test was performed in the controls. The odds ratios (OR) and 95% confidence intervals (CI) for type 2 diabetes were calculated using conditional logistic regression.ResultsThe diabetes cases had significantly less education, more first-degree relatives with a positive family history of diabetes and higher body mass index (BMI) scores compared with the controls. Also, after adjusting for possible confounders, an increased risk of type 2 diabetes was determined for current smokers (OR = 2.41; 95% CI 1.07–5.44) vs. non-smokers. In addition, there was an association between the disease and duration of smoking (OR = 2.47; 95% CI 1.03–5.93 for 40 years or more) vs. non-smokers, and those who had been smokers for 10 or more pack-years had twice the risk of diabetes (OR = 2.17; 95% CI 1.07–4.40) vs. non-smokers. There were no significant associations found between the risk of type 2 diabetes and number of cigarettes smoked per day or stopping smoking.ConclusionOur data confirms that smoking may be an independent risk factor for type 2 diabetes.     

Low-density lipoprotein cholesterol and risk of type 2 diabetes: The Isfahan diabetes prevention study

Background

Studies reported that lipid-lowering treatment may increase the risk of diabetes, support the hypothesis that low-density lipoprotein cholesterol (LDLC) may be associated with type 2 diabetes (T2D).

Prevention of type 2 diabetes: An update

With the rising tide of the diabetes epidemic leading to increased morbidity and mortality (primarily from cardiovascular disease), together with failure to control the disease and its associated complications, prevention of diabetes appears to be the logical option for curbing this epidemic. Several trials have been completed, and others ongoing, using various strategies for diabetes prevention. In this review, we provide an update on diabetes prevention strategies, highlighting the rationale behind such interventions, together with an outlook of the ongoing efforts that are likely to provide additional options for patients at risk for diabetes.     

Prevention of type 2 diabetes: a review

One of the major public health challenges of the 21st century is type 2 diabetes. WHO estimates that by 2025 as many as 200-300 million people worldwide will have developed the disease. A distressing increase in children is perhaps the most alarming sign of something going wrong. Roughly half of the risk of type 2 diabetes can be attributed to environmental exposure and the other half to genetics. Central themes for prevention are the risk factors overweight, sedentary lifestyle, certain dietary components and perinatal factors. Overweight is the most critical risk factor, and should be targeted for prevention of type 2 diabetes especially among children and youths. Ethnicity and perinatal factors are also worth considering. Today we know that prevention helps. In the US Diabetes Prevention Programme for high risk individuals, there was a 58% relative reduction in the progression to diabetes in the lifestyle group compared with the controls. Within the lifestyle group, 50% achieved the goal of more than 7% weight reduction, and 74% maintained at least 150 min of moderately intense activity each week. This review discusses different forms of prevention, and proposes first of all to target people with Impaired Glucose Tolerance with increasing activity and altering dietary factors. And secondly, population-based measures to encourage increased physical activity and decreased consumption of energy-dense foods are important, and may target school children and young people, certain ethnic groups and women with gestational diabetes.     

Association between glycaemia risk index (GRI) and diabetic retinopathy in type 2 diabetes: A cohort study

Aim

To investigate the association between a new composite metric, glycaemia risk index (GRI), and incident diabetic retinopathy (DR).

Methods

A total of 1204 adults with type 2 diabetes without DR at baseline were included between 2005 and 2019 from a single centre in Shanghai, China. GRI was obtained from continuous glucose monitoring data at baseline. Cox proportion hazard regression analysis was used to assess the association between GRI and the risk of incident DR.

Results

During a median follow-up of 8.4 years, 301 patients developed DR. The multivariable-adjusted hazard ratios (HRs) for incident DR across ascending GRI quartiles (≤14 [reference], 15 ~ 28, 29 ~ 47 and > 47) were 1.00, 1.05 (95% CI 0.74-1.48), 1.33 (95% confidence interval [CI] 0.96-1.84) and 1.53 (95% CI 1.11-2.11), respectively. For each 1-SD increase in GRI, the risk of DR was increased by 20% (HR 1.20, 95% CI 1.07-1.33) after adjustment for confounders.

Conclusions

In patients with type 2 diabetes, higher GRI is associated with an increased risk of incident DR. GRI has the potential to be a valuable clinical measure, which needs to be further explored in future studies.     

Overweight and risk of type 2 diabetes: A prospective Chinese twin study

Objectives: This study aimed to estimate the association between overweight and type 2 diabetes mellitus (T2DM) in twins, and further to explore whether genetic and early-life environmental factors account for this association.Methods: This study included 31,197 twin individuals from the Chinese National Twin Registry (CNTR). Generalized estimating equation (GEE) models were applied for unmatched case-control analysis. Conditional logistic regressions were used in co-twin matched case-control analysis. Logistic regressions were fitted to examine the differences in odds ratios (ORs) from the GEE models and conditional logistic regressions. Bivariate genetic model was used to explore the genetic and environmental correlation between body mass index (BMI) and T2DM.Results: In the GEE model, overweight was associated with a higher T2DM risk (OR=2.71, 95% confidence interval (CI): 1.96～3.73), compared with participants with normal BMI. In the multi-adjusted conditional logistic regression, the association was still significant (OR=2.60, 95% CI: 1.15～5.87). The ORs from the unmatched and matched analyses were different (P = 0.042). Particularly, overweight could increase T2DM risk in monozygotic (MZ) twins, and the difference in ORs between the unmatched and matched designs was significant (P = 0.014). After controlling for age and sex, the positive BMI-T2DM association was partly due to a significant genetic correlation (rA= 0.31, 95% CI: 0.20～0.41).Conclusions: Our findings suggest that genetics and early-life environments might account for the observed overweight-T2DM association. Genetic correlation between BMI and T2DM further provides evidence for the influence of overlap genes on their association.     

Family history of type 1 and type 2 diabetes and risk of latent autoimmune diabetes in adults (LADA)

BackgroundA family history of diabetes (FHD) is a strong predictor of diabetes risk, yet has rarely been investigated in latent autoimmune diabetes in adults (LADA). This study therefore investigated the risk of LADA and type 2 diabetes (T2D) in relation to FHD, taking into account the type of diabetes in relatives.MethodsData from a population-based study were used, including incident cases of LADA [glutamic acid decarboxylase antibody (GADA)-positive, n = 378] and T2D (GADA-negative, n = 1199), and their matched controls (n = 1484). First-degree relatives with disease onset at age < 40 years and taking insulin treatment were classified as type 1 diabetes (T1D) or, if otherwise, as T2D. Odds ratios (ORs) were adjusted for age, gender, BMI, education and smoking. Cases were genotyped for high- and low-risk HLA genotypes.ResultsBoth FHD–T1D (OR: 5.8; 95% CI: 3.2–10.3) and FHD–T2D (OR: 1.9; 95% CI: 1.5–2.5) were associated with an increased risk of LADA, whereas the risk of T2D was associated with FHD–T2D (OR: 2.7; 95% CI: 2.2–3.3), but not FHD–T1D. In LADA patients, FHD–T1D vs FHD–T2D was associated with higher GADA but lower C-peptide levels, lower prevalence of low-risk HLA genotypes (5.0% vs 28.6%, respectively; P = 0.038) and a tendency for higher prevalence of high-risk genotypes (90.0% vs 69.1%, respectively; P = 0.0576).ConclusionThe risk of LADA is substantially increased with FHD–T1D but also, albeit significantly less so, with FHD–T2D. This supports the idea of LADA as a mix of both T1D and T2D, but suggests that the genes related to T1D have greater impact. LADA patients with FHD–T1D had more T1D-like features, emphasizing the heterogeneity of LADA.     

Normal fasting plasma glucose and risk of prediabetes and type 2 diabetes: the Isfahan Diabetes Prevention Study

AIM: To determine the association of fasting plasma glucose (FPG) level within normal range and the risk of prediabetes and type 2 diabetes in an Iranian population. METHODS: A total of 806 first-degree relatives (FDRs) of patients with type 2 diabetes who had FPG levels less than 5.6 mmol/l (100 mg/dl) in 2003 to 2005, and who did not have diabetes or impaired fasting glucose (IFG), were followed through 2010 for the occurrence of prediabetes or type 2 diabetes. At baseline and through follow-ups, participants underwent a standard 75 g 2-hour oral glucose tolerance test (OGTT). RESULTS: The incidence of type 2 diabetes, impaired glucose tolerance (IGT), and IFG was 9.6 (95% confidence interval (CI): 6.8-12.4), 28.7 (23.8-33.6), and 33.0 (27.7-38.2) per 1,000 person-years based on 4,489 person-years of follow-up, respectively. FPG was associated with the incidence of diabetes, IGT, and IFG. The multivariate-adjusted hazard ratios (95% CI) for diabetes, IGT, and IFG were 1.36 (1.01-1.84), 1.45 (1.10-1.91) and 1.31 (1.00-1.71), for the highest quintile of FPG compared with the lowest quintile, respectively. CONCLUSIONS: An increase in FPG in the normal range is associated with an increase in the incidence of IGT, IFG, and type 2 diabetes. These results prove FPG in the normal range to be useful in identifying apparently healthy FDRs of patients with type 2 diabetes at risk of developing prediabetes and diabetes.