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"Diabetes Mellitus - epidemiology"
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Common Variants in 40 Genes Assessed for Diabetes Incidence and Response to Metformin and Lifestyle Intervention in the Diabetes Prevention Program
Genome-wide association studies have begun to elucidate the genetic architecture of type 2 diabetes. We examined whether single nucleotide polymorphisms (SNPs) identified through targeted complementary approaches affect diabetes incidence in the at-risk population of the Diabetes Prevention Program (DPP) and whether they influence a response to preventive interventions.
We selected SNPs identified by prior genome-wide association studies for type 2 diabetes and related traits, or capturing common variation in 40 candidate genes previously associated with type 2 diabetes, implicated in monogenic diabetes, encoding type 2 diabetes drug targets or drug-metabolizing/transporting enzymes, or involved in relevant physiological processes. We analyzed 1,590 SNPs for association with incident diabetes and their interaction with response to metformin or lifestyle interventions in 2,994 DPP participants. We controlled for multiple hypothesis testing by assessing false discovery rates.
We replicated the association of variants in the metformin transporter gene SLC47A1 with metformin response and detected nominal interactions in the AMP kinase (AMPK) gene STK11, the AMPK subunit genes PRKAA1 and PRKAA2, and a missense SNP in SLC22A1, which encodes another metformin transporter. The most significant association with diabetes incidence occurred in the AMPK subunit gene PRKAG2 (hazard ratio 1.24, 95% CI 1.09-1.40, P = 7 × 10(-4)). Overall, there were nominal associations with diabetes incidence at 85 SNPs and nominal interactions with the metformin and lifestyle interventions at 91 and 69 mostly nonoverlapping SNPs, respectively. The lowest P values were consistent with experiment-wide 33% false discovery rates.
We have identified potential genetic determinants of metformin response. These results merit confirmation in independent samples.
Journal Article
The metabolic syndrome as predictor of type 2 diabetes: The San Antonio Heart study
The oral glucose tolerance test identifies high-risk subjects for diabetes, but it is costly and inconvenient. To find better predictors of type 2 diabetes, we evaluated two different definitions of the metabolic syndrome because insulin resistance, which is commonly associated with this clustering of metabolic factors, frequently precedes the onset of type 2 diabetes.
We compared the ability of the National Cholesterol Education Program (NCEP) definition, a modified version of the 1999 World Health Organization (WHO) definition that excludes the 2-h glucose requirement, and impaired glucose tolerance (IGT) to predict incident type 2 diabetes. In the San Antonio Heart Study, 1734 participants completed a 7- to 8-year follow-up examination.
IGT and the NCEP definition had higher sensitivity than the modified WHO definition (51.9, 52.8, and 42.8%, respectively). IGT had a higher positive predictive value than the NCEP and modified WHO definitions (43.0, 30.8, and 30.4%, respectively). The combination of the IGT and NCEP definitions increased the sensitivity to 70.8% with an acceptable positive predictive value of 29.7%. Risk for incidence of type 2 diabetes using the NCEP definition was independent of other risk factors, including IGT and fasting insulin (odds ratio 3.30, 95% CI 2.27-4.80). The NCEP definition performed better with fasting glucose >or=5.4 mmol/l (sensitivity 62.0% and positive predictive value 30.9%).
The metabolic syndrome predicts diabetes independently of other factors. However, the NCEP definition performs better than the modified 1999 WHO definition. Lowering the fasting glucose cutoff to 5.4 mmol/l improves the prediction of diabetes by the metabolic syndrome.
Journal Article
Trends in the incidence of diabetes mellitus: results from the Global Burden of Disease Study 2017 and implications for diabetes mellitus prevention
Backgroud
Diabetes mellitus is a common chronic disease and a severe public health issue. The incidence trends for type 1 diabetes (TIDM) and type 2 diabetes (T2DM) have rarely been studied on a global scale. We aimed to determine the temporal and geographical trends of diabetes globally.
Methods
Data on diabetes mellitus, including incidence, prevalence from 1990 to 2017 were obtained from the 2017 Global Burden of Disease study. We calculated the estimated annual percentage changes (EAPCs) in age-standardized incidence rate (ASIR) of diabetes mellitus according to sex, region, and disease type.
Results
The worldwide incident cases of diabetes mellitus has increased by 102.9% from 11,303,084 cases in 1990 to 22,935,630 cases in 2017 worldwide, while the ASIR increased from 234 /100,000 persons (95% UI, 219–249) to 285/100,000 persons (95% UI, 262–310) in this period [EAPC = 0.87, 95% confidence interval (CI):0.79–0.96]. The global ASIRs of T1DM and T2DM both demonstrated significant increase during 1990–2017, with EAPCs of 0.34 (95% CI,0.30–0.39) and 0.89 (95% CI,0.80–0.97), respectively. The ASIR trends also varied considerably by regions and countries. The increase in ASIR was greatest in high sociodemographic index regions (EAPC = 1.05, 95% CI:0.92–1.17) and lowest in low-SDI regions (EAPC = 0.79, 95% CI:0.71–0.88).
Conclusions
Both the number of incident cases and ASIR of diabetes mellitus increased significantly during 1990–2017 worldwide, but the temporal trends varied markedly across regions and countries.
Journal Article
Telmisartan to Prevent Recurrent Stroke and Cardiovascular Events
In a multicenter trial, 20,332 patients who had recently had an ischemic stroke were randomly assigned to receive either telmisartan or placebo. All patients also received medications for blood-pressure control at the investigators' discretion. At a mean follow-up of 2.5 years, there was no significant difference between the two study groups in the rates of recurrent stroke or major cardiovascular events.
Patients who had recently had an ischemic stroke were randomly assigned to receive either telmisartan or placebo. At a mean follow-up of 2.5 years, there was no significant difference between the study groups in the rates of recurrent stroke or major cardiovascular events.
Stroke is the second most frequent cause of death in the world and is responsible for about 5 million deaths each year.
1
An additional 15 million persons have nonfatal strokes, with about a third having disabling consequences. Elevated blood pressure is the strongest risk factor for stroke, and lowering of blood pressure, especially in patients with substantially elevated levels (e.g., systolic pressure, >160 mm Hg), reduces the risk of stroke.
2
After a stroke, lowering blood pressure with a combination of an angiotensin-converting–enzyme (ACE) inhibitor and a diuretic reduced rates of recurrent stroke in the Perindopril Protection against Recurrent Stroke Study . . .
Journal Article
effects of aerobic exercise on metabolic risk, insulin sensitivity and intrahepatic lipid in healthy older people from the Hertfordshire Cohort Study: a randomised controlled trial
Aims/hypothesis We sought to determine the effect of an aerobic exercise intervention on clustered metabolic risk and related outcomes in healthy older adults in a single-centre, explanatory randomised controlled trial. Methods Participants from the Hertfordshire Cohort Study (born 1931-1939) were randomly assigned to 36 supervised 1 h sessions on a cycle ergometer over 12 weeks or to a non-intervention control group. Randomisation and group allocation were conducted by the study co-ordinator, using a software programme. Those with prevalent diabetes, unstable ischaemic heart disease or poor mobility were excluded. All data were collected at our clinical research facility in Cambridge. Components of the metabolic syndrome were used to derive a standardised composite metabolic risk score (zMS) as the primary outcome. Trial status: closed to follow-up. Results We randomised 100 participants (50 to the intervention, 50 to the control group). Mean age was 71.4 (range 67.4-76.3) years. Overall, 96% of participants attended for follow-up measures. There were no serious adverse events. Using an intention-to-treat analysis, we saw a non-significant reduction in zMS in the exercise group compared with controls (0.07 [95% CI −0.03, 0.17], p = 0.19). However, the exercise group had significantly decreased weight, waist circumference and intrahepatic lipid, with increased aerobic fitness and a 68% reduction in prevalence of abnormal glucose metabolism (OR 0.32 [95% CI 0.11-0.92], p = 0.035) compared with controls. Results were similar in per-protocol analyses. Conclusions/interpretation Enrolment in a supervised aerobic exercise intervention led to weight loss, increased fitness and improvements in some but not all metabolic outcomes. In appropriately screened older individuals, such interventions appear to be safe. Trial registration: Controlled-trials.com ISRCTN60986572 Funding: Medical Research Council
Journal Article
Web-Based Depression Treatment for Type 1 and Type 2 Diabetic Patients: A randomized, controlled trial
OBJECTIVE: Comorbid depression is common in patients with type 1 and type 2 diabetes, adversely affecting quality of life, diabetes outcomes, and mortality. Depression can be effectively treated with cognitive behavior therapy (CBT). The Internet is a new and attractive method for delivering CBT intervention on a large scale at relatively low costs. This study evaluated the effectiveness of Web-based CBT for depression treatment in adults with type 1 or type 2 diabetes, with minimal guidance. RESEARCH DESIGN AND METHODS: A randomized controlled trial was conducted in the Netherlands in 255 adult diabetic patients with elevated depressive symptoms. Primary outcomes were depressive symptoms. Secondary outcomes were diabetes-specific emotional distress and glycemic control. Assessments were at baseline, after treatment, and at the 1-month follow-up. RESULTS: The Web-based CBT was effective in reducing depressive symptoms by intention-to-treat analyses (P = 0.04, d = 0.29; clinical improvement 41% vs. 24% P < 0.001) and by per-protocol analyses (P < 0.001, d = 0.70; clinical improvement, 56% vs. 24% P < 0.001). The intervention reduced diabetes-specific emotional distress (P = 0.03) but had no beneficial effect on glycemic control (P > 0.05). CONCLUSIONS: Web-based CBT depression treatment is effective in reducing depressive symptoms in adults with type 1 and type 2 diabetes. In addition, the intervention reduces diabetes-specific emotional distress in depressed patients.
Journal Article
The changing face of paediatric diabetes
The purpose of this review is to provide an update on the changing face of paediatric type 1 diabetes and type 2 diabetes. Paediatric diabetes is on the rise, with extensive research dedicated to understanding its pathophysiology, comorbidities and complications. As obesity continues to increase among all youth, differentiating between type 1 diabetes and type 2 diabetes has become increasingly difficult but remains important for optimising treatment, anticipating complications and predicting disease risk. Novel treatments are emerging, with the ultimate goal being to achieve glycaemic control, limit weight gain, improve quality of life and reduce comorbidities. In this review, we focus on updates regarding the epidemiology, clinical presentation, comorbidities and complications of paediatric type 1 diabetes and type 2 diabetes and conclude with current and emerging treatments.
Journal Article
Web-based intervention for depressive symptoms in adults with types 1 and 2 diabetes mellitus: a health economic evaluation
Web-based interventions are effective in reducing depression. However, the evidence for the cost-effectiveness of these interventions is scarce.AimsThe aim is to assess the cost-effectiveness of a web-based intervention (GET.ON M.E.D.) for individuals with diabetes and comorbid depression compared with an active control group receiving web-based psychoeducation.
We conducted a cost-effectiveness analysis with treatment response as the outcome and a cost-utility analysis with quality-adjusted life-years (QALYs) alongside a randomised controlled trial with 260 participants.
At a willingness-to-pay ceiling of €5000 for a treatment response, the intervention has a 97% probability of being regarded as cost-effective compared with the active control group. If society is willing to pay €14 000 for an additional QALY, the intervention has a 51% probability of being cost-effective.
This web-based intervention for individuals with diabetes and comorbid depression demonstrated a high probability of being cost-effective compared with an active control group.Declaration of interestS.N., D.D.E., D.L., M.B. and B.F. are stakeholders of the Institute for Online Health Trainings, which aims to transfer scientific knowledge related to this research into routine healthcare.
Journal Article
Obstetric and perinatal outcomes in pregnancies complicated by diabetes, and control pregnancies, in Kronoberg, Sweden
Background
Diabetes during pregnancy is an increasingly common metabolic disorder, associated with significantly increased risks for both mother and child. Aim of this study was to compare maternal and perinatal outcomes in women with pregestational (PDM) type 1 (T1DM), type 2 diabetes (T2DM), gestational diabetes mellitus (GDM) and compare these to pregnancies not complicated with diabetes. This study also evaluated a specifically organized care-model mostly involving specialist diabetes nurses.
Methods
Retrospective population-based records review 2009–2012. Rates of maternal (preeclampsia, pre-term delivery, cesarean section (CS)) and fetal outcomes (large for gestational age (LGA), macrosomia, congenital malformations/intrauterine death) were assessed and potential predisposing or contributing factors as maternal age, ethnicity, obesity, weight gain, parity, HbA1c levels, insulin types and doses.
Results
Among 280 pregnancies 48 were PDM, 97 GDM and 135 without diabetes. Within the group with diabetes, early-pregnancy BMI was higher (
p
= 0.0001), pregnancy weight gain lower (11.1 ± 6.7 kg vs 13.1 ± 7.1 kg,
p
= 0.005), more delivered preterm (
p
= 0.0001), by CS (
p
= 0.05), and had more LGA neonates (
p
= 0.06) than the group without diabetes. Among pregnancies with diabetes, GDM mothers gained less weight (9.9 kg vs 13.5 kg) (
p
= 0.006), and rates of CS (
p
= 0.03), preterm deliveries (
p
= 0.001) and LGA (
p
= 0.0001) were not increased compared to PDM; More T1DM infants were LGA, 60% vs. 27% in T2DM. In pregnancies with diabetes obesity, excessive weight gain and multiparity were associated with increased risk of LGA neonates, and mother’s type of diabetes and gestational week were associated with higher rates of CS.
Conclusion
Weight gain during pregnancy was lower in pregnancies with diabetes and prevalence of LGA, CS and preterm deliveries in GDM was not elevated, also for T2DM, except increased prevalence of LGA in T1DM that warrants increased clinical attention, indicating that this model of antenatal diabetes care may have contributed to improved maternal and fetal outcomes.
Journal Article