Increased Risk Of Diabetes Research Articles

Sex differences in the association between fatty liver and type2 diabetes incidence in non-obese Japanese: A retrospective cohort study.

Aims/IntroductionAsians develop type 2 diabetes at a lower body mass index (BMI) compared with other races, which is partly because of Asian‐specific fat depots. Sex plays a role in fat deposition, regardless of race. This retrospective cohort study aimed to investigate the association among fatty liver, sex and type 2 diabetes in non‐obese Japanese.Materials and MethodsThe participants in this study (13,596 men and 6,037 women) were aged 30–64 years, and had undergone health checkups between 2013 and 2015, in Aichi, Japan. Baseline BMI was categorized as follows: <18.5, 18.5–19.9, 20–22.9, 23–24.9, 25–27.4 and ≥27.5 kg/m2. Fatty liver was diagnosed by abdominal ultrasonography. The joint effect of BMI and fatty liver on the incidence of type 2 diabetes was assessed, stratified by sex.ResultsDuring follow up, 738 men and 138 women developed type 2 diabetes. Compared with the BMI of 20–22.9 kg/m2 without fatty liver group, the BMI of 20–22.9 kg/m2 with fatty liver was associated with a higher risk of type 2 diabetes in men, but not in women. Furthermore, men with a BMI of 23–24.9 and 25–27.4 kg/m2 without fatty liver had no significant type 2 diabetes risk, whereas women with a BMI of 23–24.9 and 25–27.4 kg/m2, regardless of fatty liver, had an increased risk.ConclusionsThese results suggest the association between fatty liver and type 2 diabetes in non‐obese Asians is different by sex; fatty liver increases diabetes risk among male, not female, non‐obese Asians.

PROVIDING THE BEST PREVENTION AND TREATMENT FOR DIABETES PATIENTS

Diabetes is one of the main threats to human health in this century. The drastic increase in incidence of diabetes worldwide has been attributed to distinct changes in human behavior and lifestyle during the last century. To prevent the personal and socio-economic burden of diabetes effort to prevent the disease needs to start before the onset of diabetes and address all susceptibility factors. Four recent studies have shown that prevention of type 2 diabetes is possible and that reinforced lifestyle interventions / modification can significantly reduce the onset of the disease. The studies repeatedly showed that for about 60% of the persons with increased diabetes risk, compared to a control group, the diabetes was prevented from developing. Early pharmacologic preventive strategies have yielded 25-30%. These studies have convincingly demonstrated that the primary aim in prevention of type 2 diabetes is the stabilization of glucose tolerance due to improvement of insulin resistance. Based on the studies intervention protocol focuses on achieving 5 core goals. With respect to the world wide burden of diabetes this studies offer a compelling evidence-base for the important translation of the research findings into community-based prevention strategies a development of a National Diabetes Prevention Program.&#x0D; Key words: Diabetes Mellitus, Treatment, Prevention

Interaction Between GAD65 Antibodies and Dietary Fish Intake or Plasma Phospholipid n-3 Polyunsaturated Fatty Acids on Incident Adult-Onset Diabetes: The EPIC-InterAct Study.

OBJECTIVEIslet autoimmunity is associated with diabetes incidence. We investigated whether there was an interaction between dietary fish intake or plasma phospholipid n-3 polyunsaturated fatty acid (PUFA) concentration with the 65-kDa isoform of GAD (GAD65) antibody positivity on the risk of developing adult-onset diabetes.RESEARCH DESIGN AND METHODSWe used prospective data on 11,247 incident cases of adult-onset diabetes and 14,288 noncases from the EPIC-InterAct case-cohort study conducted in eight European countries. Baseline plasma samples were analyzed for GAD65 antibodies and phospholipid n-3 PUFAs. Adjusted hazard ratios (HRs) for incident diabetes in relation to GAD65 antibody status and tertiles of plasma phospholipid n-3 PUFA or fish intake were estimated using Prentice-weighted Cox regression. Additive (proportion attributable to interaction [AP]) and multiplicative interactions between GAD65 antibody positivity (≥65 units/mL) and low fish/n-3 PUFA were assessed.RESULTSThe hazard of diabetes in antibody-positive individuals with low intake of total and fatty fish, respectively, was significantly elevated (HR 2.52 [95% CI 1.76–3.63] and 2.48 [1.79–3.45]) compared with people who were GAD65 antibody negative and had high fish intake, with evidence of additive (AP 0.44 [95% CI 0.16–0.72] and 0.48 [0.24–0.72]) and multiplicative (P = 0.0465 and 0.0103) interactions. Individuals with high GAD65 antibody levels (≥167.5 units/mL) and low total plasma phospholipid n-3 PUFAs had a more than fourfold higher hazard of diabetes (HR 4.26 [2.70–6.72]) and an AP of 0.46 (0.12–0.80) compared with antibody-negative individuals with high n-3 PUFAs.CONCLUSIONSHigh fish intake or relative plasma phospholipid n-3 PUFA concentrations may partially counteract the increased diabetes risk conferred by GAD65 antibody positivity.

Endoplasmic reticulum stress and oxidative stress drive endothelial dysfunction induced by high selenium.

Selenium is an essential trace element important for human health. A balanced intake is, however, crucial to maximize the health benefits of selenium. At physiological concentrations, selenium mediates antioxidant, anti-inflammatory, and pro-survival actions. However, supra-nutritional selenium intake was associated with increased diabetes risk leading potentially to endothelial dysfunction, the initiating step in atherosclerosis. High selenium causes apoptosis in cancer cells via endoplasmic reticulum (ER) stress, a mechanism also implicated in endothelial dysfunction. Nonetheless, whether ER stress drives selenium-induced endothelial dysfunction, remains unknown. Here,we investigated the effects of increasing concentrations of selenium on endothelial cells. High selenite reduced nitric oxide bioavailability and impaired angiogenesis. High selenite also induced ER stress, increased reactive oxygen species (ROS) production, and apoptosis. Pretreatment with the chemical chaperone, 4-phenylbutyrate, prevented the toxic effects of selenium. Our findings support a model where high selenite leads to endothelial dysfunction through activation of ER stress and increased ROS production. These results highlight the importance of tailoring selenium supplementation to achieve maximal health benefits and suggest that prophylactic use of selenium supplements as antioxidants may entail risk.

Risk factors, incidence, and prevalence of diabetes among rural farm and non-farm residents of Saskatchewan, Canada; a population-based longitudinal cohort study.

Saskatchewan has a high prevalence of diabetes. It is the largest, rurally populated, predominantly agricultural province in Canada. This research aims to determine the risk factors associated with the incidence and longitudinal changes in the prevalence of diabetes among Saskatchewan's adult rural farm and non-farm residents. The Saskatchewan Rural Health Study (SRHS) is a prospective cohort study conducted in two phases: a baseline survey (2010, 8261 participants) and a follow-up survey (2014, 4867 participants). Generalized estimation equations and survival analysis techniques were used to determine diabetes prevalence and incidence risk factors, respectively. Incidence of diabetes among rural residents was 2.75%. Positive family history, high BMI, sleep apnea and an abnormal Epworth Sleepiness Score (ESS) were significant predictors for diabetes incidence. A substantial increase (1.98%) of diabetes prevalence was observed after four years of follow-up. Risk factors of diabetes prevalence were increasing age, male, low income, positive family history, high BMI, hypertension and heart attack. A mix of individual and contextual factors interacting in complex pathways were responsible for the high incidence and prevalence of diabetes among rural residents. The most original finding of that study was a positive association of sleep apnea, and ESS with incident diabetes warrants further research to identify a causal linkage. Increased diabetes risk among rural male insecticide users indicates an adverse consequence of unprotected chemical exposures in the agricultural field. Urgent population-based preventive measures should initiate to slow the increasing trend of diabetes prevalence among rural residents.

Per- and Polyfluoroalkyl Substances (PFAS) and Incident Diabetes in Midlife Women: Study of Women’s Health Across the Nation (SWAN)

Background: Diabetogenic effects of per- and polyfluoroalkyl substances (PFAS) have been suggested. However, evidence based on population-based prospective cohort studies is limited. We examined the association between serum PFAS concentrations and incident diabetes in the Study of Women’s Health Across the Nation (SWAN), a community-based population study of midlife women.Methods: We included 1,226 diabetes-free women aged 45-56 years at the baseline of the SWAN Multi-Pollutant Study in 1999-2000 who were followed up to 2016. Serum PFAS concentrations were quantified by online solid phase extraction-high performance liquid chromatography-isotope dilution-tandem mass spectrometry. We used k-means clustering and identified three overall PFAS concentration patterns as mixtures (low, medium, high). Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs).Results: We identified 137 incident diabetes cases (median follow-up=16 years, incident rate=8.15 per 1000 person-years). After adjustment for age, race/ethnicity, site, education, income, body mass index, smoking status, alcohol, physical activity, menopausal status and hormone use, the HRs comparing the lowest with the highest tertiles were 1.56 (95% CI: 1.15-2.11) for n-perfluorooctanoate (n-PFOA) (p-for-trend=0.004); 1.56 (95% CI: 1.19-2.14) for perfluorohexane sulfonate (PFHxS) (p-for-trend=0.001); 1.43 (95% CI: 1.05-1.95) for branched-perfluorooctane sulfonate (branched-PFOS) (p-for-trend=0.02); and 1.61 (95% CI: 1.16-2.24) for 2-(N-methyl-perfluorooctane sulfonamide) acetate (MeFOSAA) (p-for-trend=0.003). The high overall PFAS concentration mixture pattern had a significantly higher HR of 1.44 (95% CI: 1.01-2.05) compared with the low mixture pattern.Conclusions: This prospective cohort study with up to 17 years of follow-up suggests that PFAS, especially PFOA, PFHxS, and PFOS and its precursor (MeFOSAA), individually or as mixtures, may increase diabetes risk in midlife women. Reduced exposure to PFAS may be an important preventative approach to lowering population-wide diabetes risk.

Female mice exposed to low doses of dioxin during pregnancy and lactation have increased susceptibility to diet-induced obesity and diabetes

ObjectiveExposure to persistent organic pollutants is consistently associated with increased diabetes risk in humans. We investigated the short- and long-term impact of transient low-dose dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) exposure during pregnancy and lactation on glucose homeostasis and beta cell function in female mice, including their response to a metabolic stressor later in life. MethodsFemale mice were injected with either corn oil (CO; vehicle control) or 20 ng/kg/d TCDD 2x/week throughout mating, pregnancy and lactation, and then tracked for 6–10 weeks after chemical exposure stopped. A subset of CO- and TCDD-exposed dams was then transferred to a 45% high-fat diet (HFD) or remained on a standard chow diet for an additional 11 weeks to assess the long-term effects of TCDD on adaptability to a metabolic stressor. To summarize, female mice were transiently exposed to TCDD and then subsequently tracked beyond when TCDD had been excreted to identify lasting metabolic effects of TCDD exposure. ResultsTCDD-exposed dams were hypoglycemic at birth but otherwise had normal glucose homeostasis during and post-TCDD exposure. However, TCDD-exposed dams on a chow diet were modestly heavier than controls starting 5 weeks after the last TCDD injection, and their weight gain accelerated after transitioning to a HFD. TCDD-exposed dams also had an accelerated onset of hyperglycemia, impaired glucose-induced plasma insulin levels, reduced islet size, increased MAFA-ve beta cells, and increased proinsulin accumulation following HFD feeding compared to controls. Overall, our study demonstrates that low-dose TCDD exposure during pregnancy has minimal effects on metabolism during the period of active exposure, but has detrimental long-term effects on metabolic adaptability to HFD feeding. ConclusionsOur study suggests that transient low-dose TCDD exposure in female mice impairs metabolic adaptability to HFD feeding, demonstrating that dioxin exposure may be a contributing factor to obesity and diabetes pathogenesis in females.

An Early-Onset Subgroup of Type 2 Diabetes: A Multigenerational, Prospective Analysis in the Framingham Heart Study.

To assess the relation of type 2 diabetes occurring earlier (age <55 years) versus later in life to the risk of cardiovascular death and to diabetes in offspring. In the Framingham Heart Study, a community-based prospective cohort study, glycemic status was ascertained at serial examinations over six decades among 5,571 first- and second-generation participants with mortality data and 2,123 second-generation participants who initially did not have diabetes with data on parental diabetes status. We assessed cause of death in a case (cardiovascular death)-control (noncardiovascular death) design and incident diabetes in offspring in relation to parental early-onset diabetes. Among the participants in two generations (N = 5,571), there were 1,822 cardiovascular deaths (including 961 coronary deaths). The odds of cardiovascular versus noncardiovascular death increased with decreasing age of diabetes onset (P < 0.001 trend). Compared with never developing diabetes, early-onset diabetes conferred a 1.81-fold odds (95% CI 1.10-2.97, P = 0.02) of cardiovascular death and 1.75-fold odds (0.96-3.21, P = 0.07) of coronary death, whereas later-onset diabetes was not associated with greater risk for either (P = 0.09 for cardiovascular death; P = 0.51 for coronary death). In second-generation participants, having a parent with early-onset diabetes increased diabetes risk by 3.24-fold (1.73-6.07), whereas having one or both parents with late-onset diabetes increased diabetes risk by 2.19-fold (1.50-3.19). Our findings provide evidence for a diabetes subgroup with an early onset, a stronger association with cardiovascular death, and higher transgenerational transmission.

Application of new modifying models and lifestyle changes and its role in providing better treatment for diabetes mellitus

Diabetes is one of the main threats to human health in this century. The drastic increase in incidence of diabetes worldwide has been attributed to distinct changes in human behaviour and lifestyle during the last century. To prevent the personal and socio-economic burden of diabetes effort to prevent the disease needs to start before the onset of diabetes and address all susceptibility factors. Four recent studies have shown that prevention of type 2, diabetes is possible and that reinforced lifestyle interventions or modification can significantly reduce the onset of the disease. The studies repeatedly showed that for about 60% of the persons with increased diabetes risk, compared to a control group, the diabetes was prevented from developing. Early pharmacologic preventive strategies have yielded 25-30%. These studies have convincingly demonstrated that the primary aim in prevention of type 2 diabetes is the stabilization of glucose tolerance due to improvement of insulin resistance. Based on the studies intervention protocol focuses on achieving 5 core goals. With respect to the world wide burden of diabetes this studies offer a compelling evidence base for the important translation of the research findings into community-based prevention strategies a development of a National diabetes prevention program. The workgroup “diabetes prevention” at the German diabetes association together with the diabetes foundation developed a concept for a National program. To realize this, a large number of partners are necessary. For the population based implementation of such a program the intervention is primarily based on reinforced behaviour modification (lifestyle and physical activity). As add on the pharmaco prevention of type 2 diabetes will be from increasing importance.

Associations of ultra-processed food and its consumption patterns with incident type 2 diabetes

Abstract Background To study the associations of the consumption of ultra-processed food (UPF) and its underlying habitual consumption patterns with incident type 2 diabetes (T2D) in a large population-based cohort. Methods In 70 421 participants (35-70 years, 58.6% women) from the Lifelines cohort study, dietary intake was assessed with a food frequency questionnaire. Principal component analysis (PCA) was performed to derive UPF consumption patterns. UPF was related to incident diabetes with adjustments for confounders, including overall diet quality. Results During a median follow-up of 41 months, the intake of UPF was associated with higher risk of type 2 diabetes (1128 cases, OR for a 10% increment in UPF intake 1.33 [95% CI 1.26, 1.41]), and remained significant after adjustment for confounders. PCA revealed four habitual UPF consumption patterns. A pattern high in cold savory snacks (OR 1.16 [95% CI 1.09, 1.22]) and a pattern high in warm savory snacks (OR 1.15 [95% CI 1.08, 1.21]) were associated with an increased diabetes risk; a pattern high in traditional Dutch cuisine was not associated with diabetes risk (OR 1.05 [95% CI 0.97, 1.14]); while a pattern high in sweet snacks and pastries was inversely associated with diabetes risk (OR 0.82 [95% CI 0.76, 0.89]). There was a clear inverse association between diabetes risk at baseline and the sweet snacks and pastries pattern (β = -0.104 [95% CI -0.113, -0.094]). Conclusions A higher consumption of UPF was associated with higher risk of type 2 diabetes. For consumption patterns, this association was most pronounced for the patterns that were high in savory snacks. Our findings emphasize that in addition to promoting the consumption of healthy food products, discouraging the consumption of UPF, specifically savory snacks, should be considered as part of future diabetes prevention strategies. Key messages Ultra-processed foods intake was associated with increased risk of type 2 diabetes. Consumption patterns of ultra-processed foods should be the focus for future policies.

Peripancreatic adipose tissue protects against high-fat-diet-induced hepatic steatosis and insulin resistance in mice

Background/objectivesVisceral adiposity is associated with increased diabetes risk, while expansion of subcutaneous adipose tissue may be protective. However, the visceral compartment contains different fat depots. Peripancreatic adipose tissue (PAT) is an understudied visceral fat depot. Here, we aimed to define PAT functionality in lean and high-fat-diet (HFD)-induced obese mice.Subjects/methodsFour adipose tissue depots (inguinal, mesenteric, gonadal, and peripancreatic adipose tissue) from chow- and HFD-fed male mice were compared with respect to adipocyte size (n = 4–5/group), cellular composition (FACS analysis, n = 5–6/group), lipogenesis and lipolysis (n = 3/group), and gene expression (n = 6–10/group). Radioactive tracers were used to compare lipid and glucose metabolism between these four fat depots in vivo (n = 5–11/group). To determine the role of PAT in obesity-associated metabolic disturbances, PAT was surgically removed prior to challenging the mice with HFD. PAT-ectomized mice were compared to sham controls with respect to glucose tolerance, basal and glucose-stimulated insulin levels, hepatic and pancreatic steatosis, and gene expression (n = 8–10/group).ResultsWe found that PAT is a tiny fat depot (~0.2% of the total fat mass) containing relatively small adipocytes and many “non-adipocytes” such as leukocytes and fibroblasts. PAT was distinguished from the other fat depots by increased glucose uptake and increased fatty acid oxidation in both lean and obese mice. Moreover, PAT was the only fat depot where the tissue weight correlated positively with liver weight in obese mice (R = 0.65; p = 0.009). Surgical removal of PAT followed by 16-week HFD feeding was associated with aggravated hepatic steatosis (p = 0.008) and higher basal (p < 0.05) and glucose-stimulated insulin levels (p < 0.01). PAT removal also led to enlarged pancreatic islets and increased pancreatic expression of markers of glucose-stimulated insulin secretion and islet development (p < 0.05).ConclusionsPAT is a small metabolically highly active fat depot that plays a previously unrecognized role in the pathogenesis of hepatic steatosis and insulin resistance in advanced obesity.

Birth weight, childhood and adolescent growth and diabetes risk factors in 21-year-old Asian Indians: the Pune Children's Study.

Our objective was to investigate associations of body size (birth weight and body mass index (BMI)) and growth in height, body fat (adiposity) and lean mass during childhood and adolescence, with risk markers for diabetes in young South Asian adults. We studied 357 men and women aged 21 years from the Pune Children's Study birth cohort. Exposures were 1) birth weight, 21-year BMI, both of these mutually adjusted, and their interaction, and 2) uncorrelated conditional measures of growth in height and proxies for gain in adiposity and lean mass from birth to 8 years (childhood) and 8 to 21 years (adolescence) constructed from birth weight, and weight, height, and skinfolds at 8 and 21 years. Outcomes were plasma glucose and insulin concentrations during an oral glucose tolerance test and derived indices of insulin resistance and secretion. Higher 21-year BMI was associated with higher glucose and insulin concentrations and insulin resistance, and lower disposition index. After adjusting for 21-year BMI, higher birth weight was associated with lower 120-min glucose and insulin resistance, and higher disposition index. In the growth analysis, greater adiposity gain during childhood and adolescence was associated with higher glucose, insulin and insulin resistance, and lower disposition index, with stronger effects from adolescent gain. Greater childhood lean gain and adolescent height gain were associated with lower 120-min glucose and insulin. Consistent with other studies, lower birth weight and higher childhood weight gain increases diabetes risk. Disaggregation of weight gain showed that greater child/adolescent adiposity gain and lower lean and height gain may increase risk.

Metabolic Syndrome and Diabetes Risk Among Young Adult Students in the Health Sciences from Kathmandu, Nepal.

BackgroundThe widespread dissemination of unhealthy dietary habits, childhood-teenage obesity, and sedentary lifestyle in young adults has paved the way for public health burden metabolic syndrome and early onset of type 2 diabetes mellitus. The aim of this study was to assess the prevalence and risk factors for metabolic syndrome and diabetes among young adult students.MethodsThis cross-sectional study was conducted among students of age group (18 to 25 years) studying at Manmohan Memorial Institute of Health Sciences and Central Institute of Science and Technology. The diabetes risk score of each individual was calculated by the Finnish Diabetes Risk Score (FINDRISC tool). Independent risk factors for diabetes and metabolic syndrome were measured by multivariable logistic regression analysis. The p-value of <0.05 was considered statistically significant in this study.ResultsA total of 825 students were recruited and 739 (89.6%) students completed the study with all the fulfilled criteria. The metabolic syndrome (Harmonized Joint Scientific Statement (HJSS) criteria) was present in 7.1%, and the most prevalent defining component was low HDL-C (78%); 74.8% of students were under low risk, 22.18% were at slightly elevated risk, 2.02% were at moderate risk, and 1.01% were at high risk of diabetes. The cardiometabolic risk factors like BMI, TC, and LDL-C were higher at a significant level (p<0.001) with an increased diabetes risk score. Independent lifestyle risk factor for metabolic syndrome was current smoking (AOR, 4.49, 95% CI 1.38–14.62) whereas, an independent lifestyle risk factor for diabetes was low adherence to physical exercise (AOR, 4.81, 95% CI, 2.90–7.99).ConclusionMetabolic syndrome is present, although in low numbers in young adults putting them at risk to develop diabetes in the near future. Early assessment of metabolic syndrome and diabetes risk in young may provide insights for preventive and control plans for risk population.

Lifestyle and glycemic health 5\xa0years postpartum in obese and non-obese high diabetes risk women

AimWomen with prior gestational diabetes (GDM) are at increased diabetes risk. This study aimed to assess whether lifestyle is associated with glycemic health of high-risk women 5 years postpartum, taking into account the pre-pregnancy BMI.MethodsThe RADIEL study enrolled before or in early pregnancy 720 women with pre-pregnancy BMI ≥ 30 kg/m2 and/or prior GDM. The follow-up visit 5 years postpartum included questionnaires and measurements of anthropometrics, blood pressure, and physical activity (PA) as well as analyses of glucose metabolism, lipids, and inflammatory markers. We measured body composition (Inbody) and calculated a Healthy Food Intake Index (HFII) from Food Frequency Questionnaires (FFQ). ArmBand measured PA, sedentary time, and sleep. To take into account the diverse risk groups of GDM, we divided the women based on pre-pregnancy BMI over/under 30 kg/m2.ResultsAltogether 348 women attended the follow-up. The obese and non-obese women showed similar prevalence of glycemic abnormalities, 13% and 19% (p = 0.139). PA levels were higher among the non-obese women (p < 0.05), except for step count, and their HFII was higher compared to the obese women (p = 0.033). After adjusting for age, education, and GDM history, PA and HFII were associated with glycemic health only among obese women. When both lifestyle factors were in the same model, only PA remained significant. PA associated with other markers of metabolic health also among the non-obese women, excluding HbA1c.ConclusionLifestyle 5 years postpartum was associated with better glycemic health only among the obese high-risk women. PA, however, is essential for the metabolic health of all high-risk women.Clinical trial registrationClinicalTrials.gov, http://www.clinicaltrials.com, NCT01698385.

Early Life Famine Exposure, Ideal Cardiovascular Health Metrics, and Risk of Incident Diabetes: Findings From the 4C Study.

We aim to investigate the impact of ideal cardiovascular health metrics (ICVHMs) on the association between famine exposure and adulthood diabetes risk. This study included 77,925 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study who were born around the time of the Chinese Great Famine and free of diabetes at baseline. They were divided into three famine exposure groups according to the birth year, including nonexposed (1963-1974), fetal exposed (1959-1962), and childhood exposed (1949-1958). Relative risk regression was used to examine the associations between famine exposure and ICVHMs on diabetes. During a mean follow-up of 3.6 years, the cumulative incidence of diabetes was 4.2%, 6.0%, and 7.5% in nonexposed, fetal-exposed, and childhood-exposed participants, respectively. Compared with nonexposed participants, fetal-exposed but not childhood-exposed participants had increased risks of diabetes, with multivariable-adjusted risk ratios (RRs) (95% CIs) of 1.17 (1.05-1.31) and 1.12 (0.96-1.30), respectively. Increased diabetes risks were observed in fetal-exposed individuals with nonideal dietary habits, nonideal physical activity, BMI ≥24.0 kg/m2, or blood pressure ≥120/80 mmHg, whereas significant interaction was detected only in BMI strata (P for interaction = 0.0018). Significant interactions have been detected between number of ICVHMs and famine exposure on the risk of diabetes (P for interaction = 0.0005). The increased risk was observed in fetal-exposed participants with one or fewer ICVHMs (RR 1.59 [95% CI 1.24-2.04]), but not in those with two or more ICVHMs. The increased risk of diabetes associated with famine exposure appears to be modified by the presence of ICVHMs.

1349-P: Incidence of Diabetes in Women with Gestational Diabetes Mellitus Diagnosed by the IADPSG vs. Two-Step Criteria

Background: In Canada, the 2-step approach for the diagnosis of gestational diabetes (GDM) continues to be used, due to uncertain treatment benefit at the lower diagnostic thresholds recommended by the International Association of Diabetes and Pregnancy Study Groups (IADPSG). GDM diagnosed by 2 step criteria is associated with an elevated risk of subsequent diabetes; however, the impact of GDM based on IADPSG criteria on future diabetes risk is unknown. Aim: To evaluate the risk of future diabetes associated with a GDM diagnosis using the 2 step and IADPSG criteria. Methods: Using Ontario population-based databases, we evaluated the incidence of diabetes in women with a live birth recorded between April 2011 and March 2014 and available prenatal glucose tolerance test records. Women were categorized according to their prenatal glucose tolerance results as no GDM, GDM based on 2-step criteria, and GDM based on IADPSG criteria (positive by IADPSG, negative by 2 step criteria). They were followed until April 2018 for a diagnosis of diabetes. Risk of diabetes associated with GDM based on each definition was compared to no GDM using a multivariable Cox proportional hazards model. Results: Of the 104,942 women included in the study, 5,371 (5.1%) had GDM by 2 step criteria and 2,436 (2.3%) had GDM based on IADPSG criteria. There were 821 (0.78%) diabetes cases over 329 771 person-years of follow-up. After adjusting for age, body-mass index, history of GDM, gestational weight gain, birth weight, income, and ethnicity, diabetes risk was significantly higher for both GDM women by 2 step criteria (HR 14.1; 95% CI 11.7-16.9) and for GDM based on IADPSG criteria alone (HR 3.1; 95% CI:2.0-4.7) compared to no GDM. Conclusion: While the relative risk of diabetes compared to normal glucose tolerance is higher for women diagnosed with GDM using the conventional 2 step criteria, GDM based on IADPSG criteria also confers a significant 3-fold increase in diabetes risk. Disclosure B. Balaji: None. S. Read: None. H. Berger: None. D. Feig: Advisory Panel; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Medtronic. B.R. Shah: None. L. Lipscombe: None.

0539 Are Short Sleepers Uncoupled Sleepers?

Abstract Introduction While short sleep durations (&amp;lt;7h/night) are associated with increased diabetes risk, there is limited evidence that increasing the habitual sleep duration of short sleepers is either feasible, or will reliably improve metabolic health outcomes. Furthermore, in the absence of insomnia disorder, it remains unclear whether habitual short sleep mainly reflects a genetic predisposition or a lifestyle choice. In a randomized controlled study we delivered a sleep extension protocol based on CBTi principles to overweight ‘short sleepers’ at increased risk of Type II diabetes. Methods 18 male short sleepers (Mage=41.4; MBMI=29.57; baseline mean TST=5.8 h/ night) with no complaints of insomnia were randomized to the sleep extension intervention or control condition (printed sleep hygiene advice). The 6-week intervention commenced with personalized sleep re-scheduling negotiated in a 60-minute 1-to-1 session, and supported by elements of sleep hygiene, stimulus control, relaxation and cognitive strategies. Outcomes included sleep duration (actigraphy), fasting insulin, Mean Amplitude of Glycemic Excursions (MAGE) from continuous glucose monitoring, and blood pressure. Data were analyzed in linear fixed effects models including time, group and baselines values. Results Adherence to the 6-week protocol was high. Relative to controls (n=8), intervention participants (n = 10) showed a significant increase in TST (95%CI 46.91min, 101.64min, p&amp;lt;0.001; MDiff = 79.4min, p&amp;lt;0.001) and significant reductions in fasting insulin (95%CI -32.08 pmol/L, -.97.0 pmol/L; p=0.04; MDiff = -10.2 pmol/L, p=0.06); MAGE (95%CI -0.77, -0.08, p=0.02; MDiff -0.35, p=0.05) and diastolic (95%CI -22, -5, p=0.004; MDiff=-12, p=0.004); and systolic blood pressure (95%CI -20, -2, p=0.03; MDiff=-10, p=0.006). Conclusion CBTi-based sleep extension protocols offer feasible and effective lifestyle interventions in the management of metabolic health in overweight short sleepers who fit published categorization of non-complaining poor sleepers with an undeveloped insomnia identity whose subjective sleep experience and objective sleep characteristics are ‘uncoupled’. Support School of Sport, Exercise and Health Sciences, Loughborough University

The Diabetes Risk and Determinants of Transition from Metabolically Healthy to Unhealthy Phenotypes in 49,702 Older Adults: 4-Year Cohort Study.

This study aimed to assess whether metabolically healthy obesity (MHO) increases the risk of diabetes and to explore how the occurrence of metabolic disorders affects the risk of diabetes and which factors determine metabolic health. This study examined 49,702 older people without diabetes via the Binhai Health Screening Program in Tianjin. Compared with individuals with metabolic health and normal weight, the risk of diabetes was increased in older adults with MHO (hazard ratio [HR]: 1.786, 95% CI: 1.407-2.279) but was not significantly increased when metabolic health was characterized by the absence of metabolic abnormalities. The older adults who were initially affected by MHO and then converted to having an unhealthy phenotype had a higher diabetes risk than older individuals with stable and healthy normal weight (HR: 3.727, 95% CI: 2.721-5.105). Waist circumference was an independent predictor of the transition from a metabolically healthy status to an unhealthy status in all BMI categories (odds ratio: 1.059, 95% CI: 1.026-1.032). The MHO phenotype was associated with an increased incidence of diabetes in older adults. The presence of metabolic disorders in the group with MHO was associated with an increased diabetes risk and was predicted by the waist circumference at baseline.

Grip Strength Cut Points for Diabetes Risk Among Apparently Healthy U.S. Adults

Early detection screening tools are needed to aid in preventing vascular complications associated with type 2 diabetes. As low muscular strength is linked to increased diabetes risk, the purpose of this study is to establish muscular strength cut points for determining diabetes risk using a large, nationally representative U.S. Using the 2011-2012 and 2013-2014 National Health and Nutrition Examination Survey data, 5,108 participants aged 20-80 years (68.6% aged 20-50 years; young male participants, n=1,813, mean age=33.43 years; young female participants, n=1,692, mean age=33.39 years; older male participants, n=813, mean age=59.92 years; older female participants, n=790, mean age=60.45 years) and free of common diabetes comorbidities were included. Muscular strength was assessed using a handgrip dynamometer and normalized by adjusting for body weight. A logistic regression for survey data controlling for covariates was used to determine normalized grip strength cut points. Diabetes risk was determined using American Diabetes Association diagnostic criteria. Analyses were conducted in the summer of 2019. Normalized grip strength significantly predicted diabetes (p=0.0332), and the cut points for detecting diabetes risk included 0.78 (young male participants), 0.57 (young female participants), 0.68 (older male participants), and 0.49 (older female participants). The risk percentages for diabetes and estimated rates reported for all subgroups were comparable, and the risk percentages included 6.84 (95% CI=5.32, 8.36; younger male participants), 7.49 (95% CI=5.87, 9.10; younger female participants), 5.76 (95% CI=2.34, 9.19, older male participants), and 4.27 (95% CI=2.44, 6.10; older female participants). Normalized grip strength using the cut points proposed in this paper may be a useful screening tool for diabetes risk in apparently healthy, normotensive adults.

Serum Uric Acid Level as a Harbinger of Type 2 Diabetes: A Prospective Observation in Taiwan

Background: Current evidence suggests an association of uric acid with diabetes risk, but it is still unclear whether uric acid is merely a risk marker or an independent risk factor. We evaluate the impact of serum uric acid (SUA) levels on the future risk of developing type 2 diabetes, independent of other factors. Methods: A population-based cohort study was conducted among 4130 participants who were found to be free of type 2 diabetes at baseline recruitment in 2002. Baseline SUA measured in 2002 was longitudinally related to the incident type 2 diabetes that occurred during the follow-up period between 2002 and 2007. Hazard ratios (HRs) and 95% confidence intervals (CIs) derived from Cox proportional hazards models were used to quantify the association. Results: There was a graded increase in the incidence of type 2 diabetes among individuals with increasing levels of SUA. In the whole study cohort, compared to quartile 1, the multivariable-adjusted HRs (95% CIs) of type 2 diabetes in quartile 2, quartile 3, and quartile 4 were 1.69 (0.76–3.76), 1.86 (0.88–4.26), and 1.94 (1.05–4.05), respectively (P for trend = 0.004). This positive gradient for the risk of type 2 diabetes across quartiles of SUA was evident in both genders and across age groups. Conclusions: This study supports that high uric acid concentrations are associated with increased diabetes risk, independent of other known risk factors. These data expand on well-established associations between SUA level and metabolic syndrome, and extend the link to the future risk of type 2 diabetes.