Sylvia H. Ley

Prevention and management of type 2 diabetes: dietary components and nutritional strategies

In the past couple of decades, evidence from prospective observational studies and clinical trials has converged to support the importance of individual nutrients, foods, and dietary patterns in the prevention and management of type 2 diabetes. The quality of dietary fats and carbohydrates consumed is more crucial than is the quantity of these macronutrients. Diets rich in wholegrains, fruits, vegetables, legumes, and nuts; moderate in alcohol consumption; and lower in refined grains, red or processed meats, and sugar-sweetened beverages have been shown to reduce the risk of diabetes and improve glycaemic control and blood lipids in patients with diabetes. With an emphasis on overall diet quality, several dietary patterns such as Mediterranean, low glycaemic index, moderately low carbohydrate, and vegetarian diets can be tailored to personal and cultural food preferences and appropriate calorie needs for weight control and diabetes prevention and management. Although much progress has been made in development and implementation of evidence-based nutrition recommendations in developed countries, concerted worldwide efforts and policies are warranted to alleviate regional disparities.

Adipokines and Incident Type 2 Diabetes in an Aboriginal Canadian Population The Sandy Lake Health and Diabetes Project

OBJECTIVE The aim of this study was to investigate associations of adiponectin, leptin, C-reactive protein (CRP), interleukin (IL)-6, and serum amyloid A (SAA), individually or in combinations, with risk of incident type 2 diabetes in a Aboriginal Canadian [corrected] population. RESEARCH DESIGN AND METHODS Of the 606 Sandy Lake Health and Diabetes Project cohort subjects who were free of diabetes at baseline, 540 (89.1%) participated in 10-year follow-up assessments. Concentrations of fasting adiponectin, leptin, CRP, IL-6, SAA, and covariates were measured at baseline. Fasting glucose and a 75-g oral glucose tolerance test were obtained at baseline and follow-up to determine incident type 2 diabetes, defined as clinically diagnosed type 2 diabetes or as fasting plasma glucose > or =7.0 mmol/l or 2-h postload plasma glucose > or =11.1 mmol/l at follow-up. RESULTS Low adiponectin, high leptin, and low adiponectin-to-leptin ratio at baseline were associated with increased risk of incident type 2 diabetes after adjustment for age, sex, triglycerides, HDL cholesterol, hypertension, and impaired glucose tolerance (odds ratio 0.63 [95% CI 0.48-0.83], 1.50 [1.02-2.21], and 0.54 [0.37-0.77], respectively). When the models were additionally adjusted for waist circumference or BMI, however, only low adiponectin remained significantly associated with increased incident diabetes (0.68 [0.51-0.90]). Combinations of leptin, CRP, IL-6, and/or SAA with adiponectin, assessed using either the ratio or joint effects, did not improve diabetes prediction. CONCLUSIONS Low baseline adiponectin is associated with increased risk of incident type 2 diabetes independent of leptin, CRP, IL-6, SAA, and metabolic syndrome variables including obesity.

Adherence to healthy lifestyle and risk of gestational diabetes mellitus: prospective cohort study

Objective To quantify the association between a combination of healthy lifestyle factors before pregnancy (healthy body weight, healthy diet, regular exercise, and not smoking) and the risk of gestational diabetes. Design Prospective cohort study. Setting Nurses’ Health Study II, United States. Participants 20 136 singleton live births in 14 437 women without chronic disease. Main outcome measure Self reported incident gestational diabetes diagnosed by a physician, validated by medical records in a previous study. Results Incident first time gestational diabetes was reported in 823 pregnancies. Each lifestyle factor measured was independently and significantly associated with risk of gestational diabetes. The combination of three low risk factors (non-smoker, ≥150 minutes a week of moderate to vigorous physical activity, and healthy eating (top two fifths of Alternate Healthy Eating Index-2010 adherence score)) was associated with a 41% lower risk of gestational diabetes compared with all other pregnancies (relative risk 0.59, 95% confidence interval 0.48 to 0.71). Addition of body mass index (BMI) <25 before pregnancy (giving a combination of four low risk factors) was associated with a 52% lower risk of gestational diabetes compared with all other pregnancies (relative risk 0.48, 0.38 to 0.61). Compared with pregnancies in women who did not meet any of the low risk lifestyle factors, those meeting all four criteria had an 83% lower risk of gestational diabetes (relative risk 0.17, 0.12 to 0.25). The population attributable risk percentage of the four risk factors in combination (smoking, inactivity, overweight, and poor diet) was 47.5% (95% confidence interval 35.6% to 56.6%). A similar population attributable risk percentage (49.2%) was observed when the distributions of the four low risk factors from the US National Health and Nutrition Examination Survey (2007-10) data were applied to the calculation. Conclusions Adherence to a low risk lifestyle before pregnancy is associated with a low risk of gestational diabetes and could be an effective strategy for the prevention of gestational diabetes.

Metabolic syndrome and its components as predictors of incident type 2 diabetes mellitus in an Aboriginal community

Background: Risk factors for type 2 diabetes remain poorly characterized among Aboriginal Canadians. We aimed to determine the incidence of type 2 diabetes in an Aboriginal community and to evaluate prospective associations with metabolic syndrome and its components. Methods: Of 606 participants in the Sandy Lake Health and Diabetes Project from 1993 to 1995 who were free of diabetes at baseline, 540 (89.1%) participated in 10-year follow-up assessments. Baseline anthropometry, blood pressure, fasting insulin and serum lipid levels were measured. Fasting and 2-hour postload glucose levels were obtained at follow-up to determine incident cases of type 2 diabetes. Results: The 10-year cumulative incidence of diabetes was 17.5%. High adiposity, dyslipidemia, hyperglycemia, hyperinsulinemia and hypertension at baseline were associated with an increased risk of diabetes after adjustment for age and sex (all p ≤ 0.03). Metabolic syndrome had high specificity (75%–88%) and high negative predictive value (85%–87%) to correctly detect diabetes-free individuals at follow-up. It had low sensitivity (26%–48%) and low positive predictive value (29%–32%) to detect future diabetes. Metabolic syndrome at baseline was associated with incident diabetes after adjustment for age and sex, regardless of whether the syndrome was defined using the National Cholesterol Education Program criteria (odds ratio [OR] 2.03, 95% confidence interval [CI] 1.10–3.75) or the International Diabetes Federation criteria (OR 2.14, 95% CI 1.29–3.55). The association was to the same degree as that for impaired glucose tolerance assessed using the oral glucose tolerance test (OR 2.87, 95% CI 1.52–5.40; p > 0.05 for comparison of C statistics). Interpretation: Metabolic syndrome and its components can be identified with readily available clinical measures. As such, the syndrome may be useful for identifying individuals at risk of type 2 diabetes in remote Aboriginal communities.

HNF1A G319S variant, active cigarette smoking and incident type 2 diabetes in Aboriginal Canadians: a population-based epidemiological study

BackgroundIn a recent report of large-scale association analysis, a type 2 diabetes susceptibility locus near HNF1A was identified in predominantly European descent populations. A population-specific G319S polymorphism in HNF1A was previously identified in Aboriginal Canadians who have a high prevalence of type 2 diabetes. We aimed to investigate the association of the HNF1A G319S polymorphism with incident type 2 diabetes and to assess whether clinical risk variables for type 2 diabetes influence the association in an Aboriginal population.MethodsOf 606 participants who were free of diabetes at baseline in 1993-1995, 540 (89.1%) participated in 10-year follow-up assessments in 2003-2005. Fasting glucose and a 75-g oral glucose tolerance test were obtained to determine incident type 2 diabetes. Participants were genotyped for the HNF1A G319S polymorphism. Interviewers administered questionnaires on smoking behavior.ResultsThe incidence rates of type 2 diabetes were 14.2% (55/388) in major allele homozygotes and 31.2% (29/93) in minor allele carriers (p < 0.001). The HNF1A G319S carrier status was associated with incident type 2 diabetes (odds ratio [OR] 3.78 [95% CI 2.13-6.69]) after adjustment for age, sex, hypertension, triglyceride, HDL cholesterol, and waist circumference. A statistical interaction was observed between HNF1A G319S and baseline active cigarette smoking on the development of type 2 diabetes with similar adjustment (p = 0.006). When participants were stratified by baseline smoking status, HNF1A G319S carriers who were active smokers had increased risk of developing diabetes (OR 6.91 [95% CI 3.38-14.12]), while the association was attenuated to non-significance among non-smokers (1.11 [0.40-3.08]).ConclusionsThe HNF1A G319S variant is associated with incident type 2 diabetes in Aboriginal Canadians. Furthermore, cigarette smoking appears to amplify incident diabetes risk in carriers of HNF1A G319S.

Effect of macronutrient intake during the second trimester on glucose metabolism later in pregnancy

BACKGROUND Dietary intake is known to influence glucose metabolism, but there is little consensus on the optimal distribution of macronutrient intakes during pregnancy to prevent gestational diabetes (GDM). OBJECTIVE We aimed to investigate whether macronutrient intake distribution during the second trimester of pregnancy was associated with glucose metabolism later in pregnancy. DESIGN Women with singleton pregnancies and without preexisting type 1 or type 2 diabetes were included. Participants underwent a 3-h oral-glucose-tolerance test at 30 wk (95% CI: 25, 33 wk) gestation and were asked to recall their second-trimester dietary intake by using a validated food-frequency questionnaire. RESULTS Of the 205 participants, 47 (22.9%) had a diagnosis of GDM. A higher intake of saturated fat (β ± SEE: 0.059 ± 0.021; P = 0.005) and trans fat (0.381 ± 0.145; P = 0.009) as a percentage of energy and of added sugar (0.017 ± 0.007; P = 0.02) and a lower intake of vegetable and fruit fiber (-0.026 ± 0.012; P = 0.03) were individually associated with increased fasting glucose after multiple adjustment. In participants with a family history of type 2 diabetes, a higher vegetable and fruit fiber intake was associated with reduced insulin resistance (-0.100 ± 0.029; P = 0.0008) and increased insulin sensitivity (0.029 ± 0.012; P = 0.01), after similar adjustment. An increased risk (OR per 1-SD change) of GDM was associated with lower carbohydrate (0.60; 95% CI: 0.40, 0.90) and higher total fat (1.61; 95% CI: 1.06, 2.44) intakes as a percentage of energy, after similar adjustment. CONCLUSIONS Macronutrient intake during the second trimester of pregnancy was associated with a risk of abnormal glucose metabolism later in pregnancy. This finding supports the need for continued work to determine optimal prenatal nutritional strategies to prevent GDM. This trial is registered at clinicaltrials.gov as NCT01405547.

Global aetiology and epidemiology of type 2 diabetes mellitus and its complications

Globally, the number of people with diabetes mellitus has quadrupled in the past three decades, and diabetes mellitus is the ninth major cause of death. About 1 in 11 adults worldwide now have diabetes mellitus, 90% of whom have type 2 diabetes mellitus (T2DM). Asia is a major area of the rapidly emerging T2DM global epidemic, with China and India the top two epicentres. Although genetic predisposition partly determines individual susceptibility to T2DM, an unhealthy diet and a sedentary lifestyle are important drivers of the current global epidemic; early developmental factors (such as intrauterine exposures) also have a role in susceptibility to T2DM later in life. Many cases of T2DM could be prevented with lifestyle changes, including maintaining a healthy body weight, consuming a healthy diet, staying physically active, not smoking and drinking alcohol in moderation. Most patients with T2DM have at least one complication, and cardiovascular complications are the leading cause of morbidity and mortality in these patients. This Review provides an updated view of the global epidemiology of T2DM, as well as dietary, lifestyle and other risk factors for T2DM and its complications.

Association of Apolipoprotein B with Incident Type 2 Diabetes in an Aboriginal Canadian Population

BACKGROUND Expanding evidence indicates that apolipoprotein B (apo B) is superior to LDL cholesterol as a marker of vascular disease. Although traditional lipid measures are known to predict type 2 diabetes, limited data are available regarding apo B. We assessed the association of apo B with incident type 2 diabetes and compared it with traditional lipid variables as a risk predictor in aboriginal Canadians. METHODS Of an initial cohort of 606 individuals without diabetes in 1993-1995, 540 were contacted for the 10-year follow-up evaluation in 2003-2005. Fasting and 2-h postload glucose concentrations were obtained at baseline and follow-up to determine incident type 2 diabetes. Baseline fasting serum lipids were measured with standard laboratory procedures. RESULTS The cumulative 10-year incidence of type 2 diabetes was 17.5%. High concentrations of apo B, triglycerides, and LDL cholesterol, and low concentrations of HDL cholesterol were individually associated with incident type 2 diabetes in univariate analyses. Comparing C statistics of univariate models showed apo B to be a superior determinant of incident diabetes compared with LDL (P = 0.026) or HDL (P = 0.004) cholesterol. With multivariate adjustment including waist circumference, apo B (odds ratio, 1.50; 95% CI, 1.11-2.02) and triglycerides (odds ratio, 1.49; 95% CI, 1.12-1.98) remained associated with incident diabetes, whereas LDL and HDL cholesterol became nonsignificant. CONCLUSIONS The association of plasma apo B with incident type 2 diabetes and its better prediction of risk compared with LDL or HDL cholesterol suggest the potential for the use of apo B in type 2 diabetes risk communication and prevention.

Associations of prenatal metabolic abnormalities with insulin and adiponectin concentrations in human milk

BACKGROUND Emerging evidence indicates that metabolic hormones are present in human milk, but, to our knowledge, no studies have investigated the impact of maternal metabolic status assessed during pregnancy on insulin and adiponectin concentrations in milk. OBJECTIVES We aimed to investigate the associations of prenatal metabolic abnormalities with insulin and adiponectin in human milk and to compare the concentrations of these hormones in early and mature milk. DESIGN Pregnant women aged ≥20 y with intention to breastfeed and without preexisting type 1 or 2 diabetes were recruited. Participants (n = 170) underwent a 3-h oral-glucose-tolerance test at 30 wk (95% CI: 25, 33 wk) gestation and donated early (the first week postpartum) and mature (3 mo postpartum) milk. RESULTS Adiponectin and insulin concentrations in early milk were higher than those in mature milk (both P < 0.0001). Prenatal metabolic abnormalities, including higher pregravid BMI (β ± SEE: 0.053 ± 0.014; P = 0.0003) and gravid hyperglycemia (0.218 ± 0.087; P = 0.01), insulin resistance (0.255 ± 0.047; P < 0.0001), lower insulin sensitivity (-0.521 ± 0.108; P < 0.0001), and higher serum adiponectin (0.116 ± 0.029; P < 0.0001), were associated with higher insulin in mature milk after covariate adjustment. Prenatal metabolic measures were not associated with milk adiponectin, but obstetrical measures that included nulliparity (0.171 ± 0.058; P = 0.004), longer duration of gestation (0.546 ± 0.146; P = 0.0002), and unscheduled cesarean delivery (0.387 ± 0.162; P = 0.02) were associated with higher adiponectin in early milk after covariate adjustment, including the time elapsed from delivery to milk collection. CONCLUSION Maternal prenatal metabolic abnormalities are associated with high insulin concentrations in mature milk, whereas only obstetrical variables are associated with adiponectin concentrations in early milk.

Sulfonylurea Use and Incident Cardiovascular Disease Among Patients With Type 2 Diabetes: Prospective Cohort Study Among Women

OBJECTIVE Evidence is inconsistent for the association between sulfonylurea use and risk of cardiovascular disease among patients with diabetes. We aimed to prospectively evaluate this association using the Nurses’ Health Study (NHS), a well-established cohort of U.S. women with long-term follow-up. RESEARCH DESIGN AND METHODS We followed 4,902 women (mean age 68 years) with diabetes (mean duration 11 years), but without cardiovascular disease at baseline. The use of sulfonylureas and other medications was self-reported at baseline and during the follow-up period of up to 10 years. Cox proportional hazards regression models were used to estimate the relative risk (RR) and 95% CI for the association between the sulfonylurea use and incident cardiovascular disease while accounting for potential confounders, including age, diabetes duration, diabetes-related complications, other antihyperglycemic medications, BMI, lifestyle factors, family history of cardiovascular diseases, and present chronic conditions. We also applied the propensity score stratification method to address the possibility of residual confounding. RESULTS We identified 339 incident cases of cardiovascular disease, including 191 cases of coronary heart disease (CHD) and 148 cases of stroke. A longer duration of sulfonylurea use was significantly associated with a higher risk of CHD (P for trend = 0.002); the RRs for CHD were 1.24 (95% CI 0.85–1.81) for patients who used sulfonylurea therapy for 1–5 years, 1.51 (0.94–2.42) for 6–10 years, and 2.15 (1.31–3.54) for >10 years, compared with nonusers. Compared with users of metformin monotherapy, the RR for CHD was 3.27 (1.31–8.17) for those who were treated with the combination of metformin and sulfonylurea. The analysis using propensity score stratification yielded similar results. We did not observe a significant association between sulfonylurea therapy and stroke risk. CONCLUSIONS Long-term use of sulfonylureas was associated with a significantly higher risk of developing CHD among women with diabetes.