Family history of diabetes is associated with higher risk for prediabetes: a multicentre analysis from the German Center for Diabetes Research

Aims/hypothesis

Prediabetes is a collective term for different subphenotypes (impaired glucose tolerance [IGT] and/or impaired fasting glucose [IFG]) with different pathophysiologies. A positive family history for type 2 diabetes (FHD) is associated with increased risk for type 2 diabetes. We assumed that it would also associate with prediabetes, but wondered whether all subphenotypes are related to a positive family history.

Methods

In a study population of 8,106 non-diabetic individuals of European origin collected from four study centres (normal glucose tolerance, NGT n?=?5,482, IFG and/or IGT n?=?2,624), we analysed whether having at least one first degree relative with diabetes is associated with prediabetes. The analyses were performed using the same models in each population separately. Afterwards, a meta-analysis was performed.

Results

FHD was significantly associated with the risk for prediabetes (IFG and/or IGT, OR 1.40; 95% CI 1.27, 1.54). This association remained significant in multivariable logistic regression models including sex, age and BMI (OR 1.26; 95% CI 1.14, 1.40). When different prediabetic outcomes were considered separately, the association was found for isolated IFG (OR 1.37; 95% CI 1.20, 1.57), isolated IGT (OR 1.25; 95% CI 1.07, 1.46) as well as for the combination IFG+IGT (OR 1.64; 95% CI 1.40, 1.93). After stratification on BMI, association between FHD and prediabetes was seen only in non-obese individuals (BMI?<?30 kg/m²).

Conclusions/interpretation

We found that FHD is an important risk factor for prediabetes, especially for combined IGT and IFG. Its relevance seems to be more evident in the non-obese.     

Prevalence of diabetes and prediabetes (impaired fasting glucose and/or impaired glucose tolerance) in urban and rural India: Phase I results of the Indian Council of Medical Research�CINdia DIABetes (ICMR�CINDIAB) study

Aims/hypothesis

This study reports the results of the first phase of a national study to determine the prevalence of diabetes and prediabetes (impaired fasting glucose and/or impaired glucose tolerance) in India.

Methods

A total of 363 primary sampling units (188 urban, 175 rural), in three states (Tamilnadu, Maharashtra and Jharkhand) and one union territory (Chandigarh) of India were sampled using a stratified multistage sampling design to survey individuals aged ??20?years. The prevalence rates of diabetes and prediabetes were assessed by measurement of fasting and 2?h post glucose load capillary blood glucose.

Results

Of the 16,607 individuals selected for the study, 14,277 (86%) participated, of whom 13,055 gave blood samples. The weighted prevalence of diabetes (both known and newly diagnosed) was 10.4% in Tamilnadu, 8.4% in Maharashtra, 5.3% in Jharkhand, and 13.6% in Chandigarh. The prevalences of prediabetes (impaired fasting glucose and/or impaired glucose tolerance) were 8.3%, 12.8%, 8.1% and 14.6% respectively. Multiple logistic regression analysis showed that age, male sex, family history of diabetes, urban residence, abdominal obesity, generalised obesity, hypertension and income status were significantly associated with diabetes. Significant risk factors for prediabetes were age, family history of diabetes, abdominal obesity, hypertension and income status.

Conclusions/interpretations

We estimate that, in 2011, Maharashtra will have 6 million individuals with diabetes and 9.2 million with prediabetes, Tamilnadu will have 4.8 million with diabetes and 3.9 million with prediabetes, Jharkhand will have 0.96 million with diabetes and 1.5 million with prediabetes, and Chandigarh will have 0.12 million with diabetes and 0.13 million with prediabetes. Projections for the whole of India would be 62.4 million people with diabetes and 77.2 million people with prediabetes.     

Progression rates from HbA1c 6.0–6.4% and other prediabetes definitions to type 2 diabetes: a meta-analysis

Aims/hypothesis

Precise estimates of progression rates from ‘prediabetes’ to type 2 diabetes are needed to optimise prevention strategies for high-risk individuals. There is acceptance of prediabetes defined by impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), but there is some controversy surrounding HbA_1c-defined prediabetes ranges, with some favouring 6.0–6.4% (42–46 mmol/mol). Comparing progression rates between groups might aid this issue, thus we aimed to accurately estimate progression rates to diabetes from different prediabetes categories.

Methods

Meta-analysis of prospective observational studies in which participants had prediabetes at baseline (ADA-defined IFG [5.6–6.9 mmol/l], WHO-defined IFG [6.1–6.9 mmol/l], IGT (7.8–11.0 mmol/l) or raised HbA_1c [6.0–6.4%/42–46 mmol/mol]) and were followed up for incident diabetes. Incidence rates were combined using Bayesian random effects models.

Results

Overall, 70 studies met the inclusion criteria. In the six studies that used raised HbA_1c, the pooled incidence rate (95% credible interval) of diabetes was 35.6 (15.1, 83.0) per 1,000 person-years. This rate was most similar to that for ADA-defined IFG (11 studies; 35.5 [26.6, 48.0]) and was non-significantly lower than WHO-defined IFG (34 studies; 47.4 [37.4, 59.8]), IGT (46 studies, 45.5 [37.8, 54.5]) and IFG plus IGT (15 studies, 70.4 [53.8, 89.7]). Similar results were seen when the data were analysed by the criteria used to diagnose diabetes.

Conclusions/interpretation

This study provides evidence that progression rates differ by prediabetes definition, which has implications for the planning and implementation of diabetes prevention programmes. HbA_1c 6.0–6.4% might identify people at a lower diabetes risk than other prediabetes definitions, but further research is needed.     

Associations between longevity of parents and glucose regulation in their offspring: the KORA S4/F4 Study

Aims

Type 2 diabetes was less prevalent in studies of the offspring of centenarians and a separate study of nonagenarian siblings. We examined whether this reduction would also be found when less extreme criteria of parental longevity (a lifespan of at least 80 years) were applied. Moreover, we looked for an association between parental longevity and incidence of dysglycaemia, which has not yet been reported for a population-based study group.

Methods

Baseline and 7-year follow-up data on 55–74-year-old participants in the population-based German Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 cohort study were used for the analyses. Participants whose parents had died from traumatic causes were excluded. Diabetes was assessed by validated physician diagnosis or OGTTs. Using logistic regression models, adjusted OR and 95% CIs were calculated for the associations between parental longevity and the prevalence or incidence of dysglycaemia, which was defined as including either type 2 diabetes or prediabetes (defined in this study as comprising impaired glucose tolerance [IGT] and impaired fasting glucose [IFG]).

Results

In age- and sex-adjusted models, the prevalence of type 2 diabetes was lower in individuals with one (OR 0.63, 95% CI 0.43, 0.93) or two (OR 0.46, 95% CI 0.25, 0.85) long-lived parents. Among participants with normal glucose tolerance at baseline, the odds of incident dysglycaemia were lower in those with one (OR 0.65, 95% CI 0.40, 1.03) or two long-lived parents (OR 0.46, 95% CI 0.22, 0.96) after adjustment for age and sex.

Conclusions/interpretation

This study showed that longevity of the parents, defined by a lifespan of at least 80 years, was associated with a lower prevalence and incidence of dysglycaemia in their offspring in an older German population.     

High prevalence of prediabetes and diabetes in a population exposed to high levels of an organochlorine cocktail

Aims/hypothesis

A heavily polluted area of Eastern Slovakia was targeted by the PCBRISK cross-sectional survey to search for possible links between environmental pollution and both prediabetes and diabetes.

Methods

Associations of serum levels of five persistent organic pollutants (POPs), namely polychlorinated biphenyls (PCBs), 2,2′-bis(4-chlorophenyl)-1,1-dichloroethylene (p,p′-DDE), 2,2′-bis(4-chlorophenyl)-1,1,1-trichloro-ethane (p,p′-DDT), hexachlorobenzene (HCB) and β-hexachlorocyclohexane (β-HCH), with prediabetes and diabetes were investigated in 2,047 adults. Diabetes and prediabetes were diagnosed by fasting plasma glucose in all participants and by OGTT in 1,220 compliant participants.

Results

Our population was stratified in terms of individual POPs quintiles and associations between environmental pollution, prediabetes and diabetes were investigated. Prevalence of prediabetes and diabetes increased in a dose-dependent manner, with individuals in upper quintiles of individual POPs showing striking increases in prevalence of prediabetes as shown by OR and 95% CI for PCBs (2.74; 1.92–3.90), DDE (1.86; 1.17–2.95), DDT (2.48; 1.77–3.48), HCB (1.86; 1.7–2.95) and β-HCH (1.97; 1.28–3.04). Interestingly, unlike PCBs, DDT and DDE, increased levels of HCB and β-HCH seemed not to be associated with increased prevalence of diabetes. Nevertheless, individuals in the 5th quintile of the variable expressing the cumulative effect of all five POPs (sum of orders) had a more than tripled prevalence of prediabetes and more than six times higher prevalence of diabetes when compared with the 1st referent quintile.

Conclusions/interpretation

Increasing serum concentrations of individual POPs considerably increased prevalence of prediabetes and diabetes in a dose-dependent manner. Interaction of industrial and agricultural pollutants in increasing prevalence of prediabetes or diabetes is likely.     

Low serum potassium levels and risk of type 2 diabetes: the Toranomon Hospital Health Management Center Study 1 (TOPICS 1)

Aims/hypothesis

Evidence has suggested that low serum potassium concentrations decrease insulin secretion, leading to glucose intolerance, and that hypokalaemia induced by diuretics increases the risk for diabetes in hypertensive individuals. However, no prospective study has investigated the association between serum potassium and the development of type 2 diabetes in a healthy cohort comprised of Asian individuals not being administered antihypertensive medications. This study aimed to investigate whether low serum potassium is associated with increased risk of type 2 diabetes in apparently healthy Japanese men.

Methods

We followed 4,409 Japanese men with no history of diabetes, use of antihypertensives, renal dysfunction or liver dysfunction (mean ± SD age, 48.4?±?8.4?years). Cox proportional hazards regression was used to estimate HRs for incident diabetes (fasting plasma glucose level ??7.0?mmol/l, HbA_1c ???6.5% or self-reported) including serum potassium concentration as either a categorical or a continuous variable.

Results

During a 5?year follow-up, 250 individuals developed type 2 diabetes. The lowest tertile of serum potassium (2.8?C3.9?mmol/l) was independently associated with the development of diabetes after adjustment for known predictors (HR 1.57 [95% CI, 1.15?C2.15]) compared with the highest tertile (4.2?C5.4?mmol/l). Every 0.5?mmol/l lower increment in the baseline serum potassium level was associated with a 45% (12?C87%) increased risk of diabetes.

Conclusions/interpretation

Mild to moderately low serum potassium levels, within the normal range and without frank hypokalaemia, could be predictive of type 2 diabetes in apparently healthy Japanese men.     

Diabetes, prediabetes and cancer mortality

Aims/hypothesis

We aimed to investigate the risk of cancer mortality in relation to the glucose tolerance status classified according to the 2 h OGTT.

Methods

Data from 17 European population-based or occupational cohorts involved in the DECODE study comprising 26,460 men and 18,195 women aged 25–90 years were collaboratively analysed. The cohorts were recruited between 1966 and 2004 and followed for 5.9 to 36.8 years. Cox proportional hazards analysis with adjustment for cohort, age, BMI, total cholesterol, blood pressure and smoking status was used to estimate HRs for cancer mortality.

Results

Compared with people in the normal glucose category, multivariable adjusted HRs (95% CI) for cancer mortality were 1.13 (1.00, 1.28), 1.27 (1.02, 1.57) and 1.71 (1.35, 2.17) in men with prediabetes, previously undiagnosed diabetes and known diabetes, respectively; in women they were 1.11 (0.94, 1.30), 1.31 (1.00, 1.70) and 1.43 (1.01, 2.02), respectively. Significant increases in deaths from cancer of the stomach, colon–rectum and liver in men with prediabetes and diabetes, and deaths from cancers of the liver and pancreas in women with diabetes were also observed. In individuals without known diabetes, the HR (95% CI) for cancer mortality corresponding to a one standard deviation increase in fasting plasma glucose was 1.06 (1.02, 1.09) and in 2 h plasma glucose was 1.07 (1.03, 1.11).

Conclusions/interpretation

Diabetes and prediabetes were associated with an increased risk of cancer death, particularly death from liver cancer. Mortality from all cancers rose linearly with increasing glucose concentrations.     

Serum magnesium and the risk of prediabetes: a population-based cohort study

Aims/hypothesis

Previous studies have found an association between serum magnesium and incident diabetes; however, this association may be due to reverse causation, whereby diabetes may induce urinary magnesium loss. In contrast, in prediabetes (defined as impaired fasting glucose), serum glucose levels are below the threshold for urinary magnesium wasting and, hence, unlikely to influence serum magnesium levels. Thus, to study the directionality of the association between serum magnesium levels and diabetes, we investigated its association with prediabetes. We also investigated whether magnesium-regulating genes influence diabetes risk through serum magnesium levels. Additionally, we quantified the effect of insulin resistance in the association between serum magnesium levels and diabetes risk.

Methods

Within the population-based Rotterdam Study, we used Cox models, adjusted for age, sex, lifestyle factors, comorbidities, kidney function, serum levels of electrolytes and diuretic use, to study the association between serum magnesium and prediabetes/diabetes. In addition, we performed two mediation analyses: (1) to study if common genetic variation in eight magnesium-regulating genes influence diabetes risk through serum magnesium levels; and (2) to quantify the proportion of the effect of serum magnesium levels on diabetes that is mediated through insulin resistance (quantified by HOMA-IR).

Results

A total of 8555 participants (mean age, 64.7 years; median follow-up, 5.7 years) with normal glucose levels (mean?±?SD: 5.46?±?0.58 mmol/l) at baseline were included. A 0.1 mmol/l decrease in serum magnesium level was associated with an increase in diabetes risk (HR 1.18 [95% CI 1.04, 1.33]), confirming findings from previous studies. Of interest, a similar association was found between serum magnesium levels and prediabetes risk (HR 1.12 [95% CI 1.01, 1.25]). Genetic variation in CLDN19, CNNM2, FXYD2, SLC41A2, and TRPM6 significantly influenced diabetes risk (p?<?0.05), and for CNNM2, FXYD2, SLC41A2 and TRPM6 this risk was completely mediated by serum magnesium levels. We found that 29.1% of the effect of serum magnesium levels on diabetes was mediated through insulin resistance, whereas for prediabetes 13.4% was mediated through insulin resistance.

Conclusions/interpretation

Low serum magnesium levels are associated with an increased risk of prediabetes and this increased risk is similar to that of diabetes. Furthermore, common variants in magnesium-regulating genes modify diabetes risk through serum magnesium levels. Both findings support a potential causal role of magnesium in the development of diabetes, where the hypothesised pathway is partly mediated through insulin resistance.

     

Which is more important for cardiometabolic health: sedentary time,higher intensity physical activity or cardiorespiratory fitness? The Maastricht Study

Aims/hypotheses

Our aim was to examine the independent and combined (cross-sectional) associations of sedentary time (ST), higher intensity physical activity (HPA) and cardiorespiratory fitness (CRF) with metabolic syndrome and diabetes status.

Methods

In 1933 adults (aged 40–75 years) ST and HPA (surrogate measure for moderate to vigorous physical activity) were measured with the activPAL3. CRF was assessed by submaximal cycle–ergometer testing. Metabolic syndrome was defined according to the Adult Treatment Panel (ATP) III guidelines. Diabetes status (normal, prediabetes [i.e. impaired glucose tolerance and/or impaired fasting glucose] or type 2 diabetes) was determined from OGTT. (Multinomial) logistic regression analyses were used to calculate likelihood for the metabolic syndrome, prediabetes and type 2 diabetes according to ST, HPA and CRF separately and combinations of ST–CRF and HPA–CRF.

Results

Higher ST, lower HPA and lower CRF were associated with greater odds for the metabolic syndrome and type 2 diabetes independently of each other. Compared with individuals with high CRF and high HPA (CRF_high–HPA_high), odds for the metabolic syndrome and type 2 diabetes were higher in groups with a lower CRF regardless of HPA. Individuals with low CRF and low HPA (CRF_low–HPA_low) had a particularly high odds for the metabolic syndrome (OR 5.73 [95% CI 3.84, 8.56]) and type 2 diabetes (OR 6.42 [95% CI 3.95, 10.45]). Similarly, compared with those with high CRF and low ST (CRF_high–ST_low), those with medium or low CRF had higher odds for the metabolic syndrome, prediabetes and type 2 diabetes, irrespective of ST. In those with high CRF, high ST was associated with significantly high odds for the metabolic syndrome (OR 2.93 [95% CI 1.72, 4.99]) and type 2 diabetes (OR 2.21 [95% CI 1.17, 4.17]). The highest odds for the metabolic syndrome and type 2 diabetes were observed in individuals with low CRF and high ST (CRF_low–ST_high) (OR [95% CI]: the metabolic syndrome, 9.22 [5.74, 14.80]; type 2 diabetes, 8.38 [4.83, 14.55]).

Conclusions/interpretation

These data suggest that ST, HPA and CRF should all be targeted in order to optimally reduce the risk for the metabolic syndrome and type 2 diabetes.

     

Prediabetes is associated with microalbuminuria,reduced kidney function and chronic kidney disease in the general population: The KORA (Cooperative Health Research in the Augsburg Region) F4-Study

Background and Aims

We investigated the associations of serum fasting (FG) and 2-h postload (2HG) glucose from an oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), fasting insulin and the homeostasis model assessment-insulin resistance index (HOMA-IR) with urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR).

Calcium and phosphate concentrations and future development of type 2 diabetes: the Insulin Resistance Atherosclerosis Study

Aims/hypothesis

Low phosphate and high calcium concentrations have been linked to altered glucose tolerance and reduced insulin sensitivity in non-diabetic individuals. The aim of this study was to examine the relationships of calcium and phosphate levels and the calcium–phosphate product with the development of type 2 diabetes.

Methods

Participants were 863 African-Americans, Hispanics and non-Hispanic whites in the Insulin Resistance Atherosclerosis Study who were free of diabetes at baseline. The mean follow-up period was 5.2 years. The insulin sensitivity index (S_I) and acute insulin response (AIR) were directly measured using the frequently sampled IVGTT.

Results

Calcium concentration (OR per 1 SD unit increase, 1.26 [95% CI 1.04, 1.53]) and calcium–phosphate product (OR 1.29 [95% CI 1.04, 1.59]) were associated with incident diabetes after adjustment for demographic variables, family history of diabetes, and 2 h glucose. The relationship between phosphate concentration and progression to diabetes was close to statistical significance (OR 1.21 [95% CI 0.98, 1.49]). Calcium concentration (OR 1.37 [95% CI 1.09, 1.72]) and calcium–phosphate product (OR 1.39 [95% CI 1.09, 1.77]) remained associated with incident diabetes after additional adjustment for BMI, plasma glucose, S_I, AIR, C-reactive protein, estimated GFR, diuretic drugs and total calcium intake.

Conclusions/interpretation

Elevated serum calcium and calcium–phosphate product are associated with increased risk of developing type 2 diabetes independently of measured glucose, insulin secretion and insulin resistance. Future studies need to analyse the role of calcium–phosphate homeostasis in the pathophysiology of diabetes.     

Awareness,Treatment and Control of Hypertension Among Filipino Immigrants

BACKGROUND

Filipino Americans have high rates of hypertension, yet little research has examined hypertension awareness, treatment, and control in this group.

OBJECTIVE

In a community-based sample of hypertensive Filipino American immigrants, we identify 1) rates of hypertension awareness, treatment, and control; and 2) factors associated with awareness, treatment, and control.

DESIGN

Cross-sectional analysis of survey data from health screenings collected from 2006 to 2010.

PARTICIPANTS

A total of 566 hypertensive Filipino immigrants in New York City, New York and Jersey City, New Jersey.

MAIN MEASURES

Hypertension awareness, treatment, and control. Participants were included in analysis if they were hypertensive, based on: a past physician diagnosis, antihypertensive medication use, and/or high blood pressure (BP) screening measurements. Demographic variables included sex, age, time in the United States, location of residence, and English spoken language fluency. Health-related variables included self-reported health, insurance status, diabetes diagnosis, high cholesterol diagnosis, clinical measures (body mass index [BMI], glucose, and cholesterol), exercise frequency, smoking status, cardiac event history, family history of cardiac event, and family history of hypertension.

RESULTS

Among the hypertensive individuals, awareness, treatment, and control rates were suboptimal; 72.1 % were aware of their status, 56.5 % were on medication, and only 21.7 % had controlled BP. Factors related to awareness included older age, worse self-reported health, family history of hypertension, and a diagnosis of high cholesterol or diabetes; factors related to treatment included older age, longer time lived in the United States, and being a non-smoker; having health insurance was found to be the main predictor of hypertension control. Many individuals had other cardiovascular disease (CVD) risk factors; 60.4 % had a BMI ≥25, 12.0 % had at-risk glucose measurements and 12.8 % had cholesterol ≥ 240.

CONCLUSIONS

Hypertensive Filipinos exhibit poor hypertension management, warranting increased efforts to improve awareness, treatment and control. Culturally tailored public health strategies must be prioritized to reduce CVD risk factors among at-risk minority populations.     

Prediabetes and the risk of cancer: a meta-analysis

Aims/hypothesis

The results from prospective cohort studies of prediabetes (impaired fasting glucose and/or impaired glucose tolerance) and risk of cancer are controversial. We conducted a meta-analysis to evaluate the risk of cancer in association with impaired fasting glucose and impaired glucose tolerance.

Methods

The PubMed, EMBASE and Cochrane Library databases were searched for prospective cohort studies with data on prediabetes and cancer. Two independent reviewers assessed the reports and extracted the data. Prospective studies were included if they reported adjusted RRs with 95% CIs for the association between cancer and prediabetes. Subgroup analyses were conducted according to endpoint, age, sex, ethnicity, duration of follow-up and study characteristics.

Results

Data from 891,426 participants were derived from 16 prospective cohort studies. Prediabetes was associated with an increased risk of cancer overall (RR 1.15; 95% CI 1.06, 1.23). The results were consistent across cancer endpoint, age, duration of follow-up and ethnicity. There was no significant difference for the risk of cancer with different definitions of prediabetes. In a site-specific cancer analysis, prediabetes was significantly associated with increased risks of cancer of the stomach/colorectum, liver, pancreas, breast and endometrium (all p?p?=?0.01) and were highest for liver, endometrial and stomach/colorectal cancer.

Conclusions/interpretation

Overall, prediabetes was associated with an increased risk of cancer, especially liver, endometrial and stomach/colorectal cancer.     

ADAMTS13 activity as a novel risk factor for incident type 2 diabetes mellitus: a population-based cohort study

Aims/hypothesis

ADAMTS13 is a protease that breaks down von Willebrand factor (VWF) multimers into smaller, less active particles. VWF has been associated with an increased risk of incident type 2 diabetes mellitus. Here, we determine whether ADAMTS13 activity and VWF antigen are associated with incident diabetes.

Methods

This study included 5176 participants from the Rotterdam Study, a prospective population-based cohort study. Participants were free of diabetes at baseline and followed up for more than 20 years. Cox proportional hazards models were used to examine the association of ADAMTS13 activity and VWF antigen with incident diabetes.

Results

ADAMTS13 activity was associated with an increased risk of incident diabetes (HR 1.17 [95% CI 1.08, 1.27]) after adjustment for known risk factors and VWF antigen levels. Although ADAMTS13 activity was positively associated with fasting glucose and insulin, the association with incident diabetes did not change when we adjusted for these covariates. ADAMTS13 activity was also associated with incident prediabetes (defined on the basis of both fasting and non-fasting blood glucose) after adjustment for known risk factors (HR 1.11 [95% CI 1.03, 1.19]), while the VWF antigen level was not. VWF antigen was associated with incident diabetes, but this association was attenuated after adjustment for known risk factors.

Conclusions/interpretation

ADAMTS13 activity appears to be an independent risk factor for incident prediabetes and type 2 diabetes. As the association between ADAMTS13 and diabetes did not appear to be explained by its cleavage of VWF, ADAMTS13 may have an independent role in the development of diabetes.

     

A former career as a male elite athlete—does it protect against type 2 diabetes in later life?

Aims/hypothesis

The aim of this study was to determine the prevalence of impaired glucose regulation in male Finnish former elite athletes and age- and area-matched controls. We hypothesised that vigorous physical activity during young adulthood protects from disturbances in glucose regulation in later life.

Methods

In 2008, 392 former male elite athletes (mean age 72.7?±?6.1 years) and 207 controls (mean age 71.6?±?5.6 years) participated in a clinical study (participation rate: 50.6%). The former athletes were divided into three groups based on their active career sport: endurance, mixed and power sports. Participants without a history of diabetes (n?=?537) underwent a 2 h 75 g OGTT. Current volume of leisure-time physical activity (LTPA) was determined by self-reported questionnaires and expressed in metabolic equivalent hours (MET-h). Data on reimbursable diabetes medication from participants and non-participants was obtained from the register of the Finnish Social Insurance Institution.

Results

Compared with the controls, the former elite athletes had a significantly lower risk of type 2 diabetes (OR 0.72, 95% CI 0.53, 0.98). The risk of type 2 diabetes decreased with increased LTPA volume (OR 0.98, 95% CI 0.97, 0.99 per 1 MET-h/week). The former elite athletes also had a significantly lower risk of impaired glucose tolerance (IGT) than the controls (OR 0.58, 95% CI 0.38, 0.87).

Conclusions/interpretation

A former career as an elite athlete protected from both type 2 diabetes and IGT in later life. In addition, the volume of current LTPA was inversely associated with the prevalence of type 2 diabetes.     

Effects of diabetes and hypertension on macrophage infiltration and matrix expansion in the rat kidney

Background

In experimental models of diabetes mellitus, aggravation of renal injury by concomitant hypertension has been described. Inflammatory mechanisms contribute to renal damage in both diseases. We investigated whether hypertension and diabetes mellitus act synergistically to induce macrophage infiltration and matrix expansion in the kidney.

Methods

Insulin-dependent diabetes mellitus was induced by streptozotocin injections to hypertensive mRen2-transgenic rats (TGR) and normotensive Sprague-Dawley control rats. Quantitative immunohistochemical examination of kidney tissue sections was used to measure macrophage infiltration and matrix expansion. The expression of MCP-1, Osteopontin, RANTES, ICAM-1 and VCAM-1 was evaluated by real-time RT-PCR. The localization of MCP-1 was studied by immunohistochemistry.

Results

Macrophage infiltration was present in the kidney of normotensive diabetic rats. Hypertensive rats exhibited a more marked infiltration of macrophages, regardless of whether diabetes was present or not. Gene expression of ICAM-1, VCAM-1 and RANTES was unaltered whereas Osteopontin and MCP-1 were induced by hypertension. Immunoreactive MCP-1 was slightly increased in diabetic rat kidney podocytes, and more markedly increased in hypertensive animals. Glomerular matrix accumulation was induced by diabetes and hypertension to a similar degree, and was highest in hypertensive, diabetic animals.

Conclusion

Diabetes mellitus caused a mild, and angiotensin-dependent hypertension a more marked infiltration of macrophages in the kidney. Combination of both diseases led to additive effects on matrix expansion but not on inflammation. Hypertension appears to be a much stronger stimulus for inflammation of the kidney than STZ diabetes, at least in mRen2-transgenic rats.     

Angiotensin converting enzyme inhibitors for prevention of new-onset type 2 diabetes mellitus: A meta-analysis of 72,128 patients

Backgroud

Angiotensin converting enzyme inhibitors (ACEIs) have been linked to reduced risk of new-onset diabetes, but the evidence was insufficient.

Objective and methods

The aim of this study was to evaluate the effect of ACEIs on the development of new-onset type 2 diabetes. Randomized controlled trials (RCTs) about ACEIs and new-onset diabetes were identified by electronic and manual searches.

Results

Nine RCTs with 92,404 patients (72,128 non-diabetic patients at baseline) were included in this study. Compared with control group, incidence of new-onset diabetes was significantly reduced in the ACEIs group [OR 0.80, (0.71, 0.91)], irrespective of achieved blood pressure levels at the follow-up. ACEIs therapy was associated with significant reduction in the risk of new-onset diabetes compared with beta-blockers/diuretics [OR 0.78, (0.65, 0.93)], placebo [OR 0.79, (0.64, 0.96)], or calcium channel blockers [OR 0.85, (0.73, 0.99)]. ACEIs treatment was associated with significant reduction in the risk of new-onset diabetes in patients with hypertension [OR 0.80, (0.68, 0.93)], coronary artery disease (CAD) or cardiovascular disease [OR 0.83, (0.68, 1.00)], or heart failure [OR 0.22, (0.10, 0.47)]. Among patients with impaired glucose tolerance or impaired fasting glucose, ramipril did not significantly reduce the incidence of diabetes [OR 0.91, (0.79, 1.05)], but significantly increased regression to normoglycemia.

Conclusion

ACEIs have beneficial effects in preventing new-onset diabetes. ACEIs provide additional benefits of lowering the risk of new-onset diabetes in patients with hypertension, CAD or other cardiovascular disease.     

Screening for diabetes using an oral glucose tolerance test within a western multi-ethnic population identifies modifiable cardiovascular risk: the ADDITION-Leicester study

Aims/hypothesis

The aim of this study was to determine the frequency of undiagnosed glucose abnormalities and the burden of cardiovascular disease (CVD) risk among south Asians and white Europeans attending a systematic screening programme for type 2 diabetes (ADDITION-Leicester) and to estimate the achievable risk reduction in individuals identified with glucose disorders.

Methods

Random samples of individuals (n?=?66,320) from 20 general practices were invited for a 75?g OGTT and CVD risk assessment. Ten-year CVD risk among screen-detected people with diabetes or impaired glucose regulation (IGR) (impaired fasting glycaemia and/or impaired glucose tolerance [IGT]) was computed using the Framingham-based ETHRISK engine and achievable risk reduction was predicted using relative reductions for treatments extracted from published trials.

Results

A total of 6,041 participants (48% male, 22% south Asian) aged 40?C75?years inclusive were included. Undiagnosed glucose disorders occurred more frequently in south Asians than white Europeans; age and sex adjusted odds ratios were 1.74 (95% CI 1.42?C2.13) and 2.30 (95% CI 1.68?C3.16) for IGT and diabetes respectively. Prevalence of any undetected glucose disorder was 17.5% in the whole cohort. Adjusted 10-year risk was similar in screen-detected people with IGR and diabetes (18.3% vs 21.6%), and was higher in south Asians across the glucose spectrum. Absolute CVD risk reductions of up to 13% in those with screen-detected type 2 diabetes and 6% in IGR are achievable using existing cardioprotective therapies.

Conclusions/interpretation

Population screening with an OGTT identifies a significant burden of modifiable CVD risk, especially within south Asian groups. Strategies enticing this population to consider screening programmes are urgently needed as significant risk reduction is possible once a glucose abnormality is identified.

Trial registration:

ClinicalTrials.gov NCT00318032

Funding:

The project is funded for support and treatment costs by NHS Department of Health Support for Science and project grants.     

Gestational retinal microvasculature and the risk of 5 year postpartum abnormal glucose metabolism

Aims/hypothesis

Changes in retinal microvasculature may reflect insulin resistance. We examined the association of changes in retinal microvasculature during pregnancy and risk of subsequent abnormal glucose metabolism in a cohort of mothers at baseline and 5 years postpartum.

Methods

Of the participants from the Singapore birth cohort (Growing Up in Singapore Towards Healthy Outcomes [GUSTO]), 276 mothers attended both baseline (at 26–28 weeks of gestation) and follow-up (5 year postpartum) visits. At baseline we performed retinal photography and assessed retinal microvascular variables using a validated grading system. At follow-up, we assessed glucose tolerance using a 75 g OGTT. We defined abnormal glucose metabolism if participants: (1) had onset of gestational diabetes mellitus (GDM) in subsequent pregnancies within a 5 year follow-up period (n = 103) or (2) had prediabetes (impaired fasting glucose, impaired glucose tolerance or HbA_1c 5.7–6.4% [39–46 mmol/mol]) and diabetes diagnosed at the 5 year follow-up visit (n = 84), according to WHO guidelines.

Results

The incidence of GDM in subsequent pregnancy and abnormal glucose metabolism 5 years postpartum was 25.2% and 30.4%, respectively. Each 10 μm widening in retinal venular calibre was associated with a significant risk of postpartum abnormal glucose metabolism (RR 1.2 [95% CI 1.0, 1.5]), independent of maternal age, college education, ethnicity, pre-pregnancy BMI and GDM at baseline. Narrower retinal arteriolar calibre and venular branching angle at baseline was associated with a higher insulin resistance index (1.4 [95% CI 1.1, 1.7] and 1.3 [95% CI 1.1, 1.6], respectively) at follow-up.

Conclusions/interpretation

Retinal microvasculature in pregnant women was associated with abnormal glucose metabolism 5 years postpartum. Alteration of microvascular structure during pregnancy may signal subclinical changes that underlie the development of prediabetes and diabetes.

     

Screening auf Typ-2-Diabetes

Background

The National Plan for Action on Diabetes proposed screening for impaired glucose tolerance (IGT) using an oral glucose tolerance test (oGTT) as IGT is associated with increased total mortality. Approximately 7?% of the population in Germany has undiagnosed diabetes and IGT.

Aim

The study aimed at investigating whether recognition of this“hidden group” with IGT is of benefit to those affected, whether the oGTT is suitable for this purpose, whether general oGTT screening can cause secondary problems and what alternative strategies could be used for identification of affected persons.

Material and method

A selective search on diabetes screening and test characteristics as well on the predictive power of the oral glucose tolerance test was carried out.

Results

The evidence for the benefits of diabetes and IGT screening regarding mortality and cardiovascular morbidity is inconclusive. Interventions concerning IGT could only show a delay in the occurrence of manifest diabetes. An advantage of screening compared to case finding could not be found. The reliability and validity of the oGTT are poor. The oGGT is of little relevance in general practice because of the high proportion of false positive findings and subsequent lack of resulting changes in lifestyle.

Conclusion

False positive findings in oGTT count as negative side effects of an intervention in the life of actually healthy people. Negative findings in the test can give rise to a motivation for an unhealthy lifestyle.