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Background: To determine whether historic albuminuria measurements provide additional predictive value for diabetic end-stage renal disease (ESRD) and natural mortality over the most recent measurement, ie, whether "regression" from high albuminuria has a different prognosis than stability at the lower level.Study Design: Observational longitudinal study.Setting& Participants: Pima Indians 15 years or older with type 2 diabetes and at least 2 consecutive measurements of urinary albumin-creatinine ratio (ACR) within 6 years.Predictors: Sequential measurements of urinary ACR.Outcomes& Measurements: Proportional hazards analyses were used to estimate the risk of ESRD and natural death associated with the first and second ACR measurement. The ability of these highly correlated variables to predict outcome was compared with receiver operating characteristic curves calculated by means of the generalized c statistic.Results: In 983 subjects, 136 developed ESRD and 180 died of natural causes during a maximum follow-up of 12.6 years. Each doubling in the second ACR was associated with a 1.71-fold greater incidence of ESRD (95% confidence interval, 1.54 to 1.89) and 1.16-fold greater natural mortality (95% confidence interval, 1.07 to 1.27) adjusted for age, sex, diabetes duration, and antihypertensive medication. The addition of the first ACR measurement to the model did not add to the predictive value for ESRD or mortality. In pairwise comparisons of c statistics, the second ACR was a significantly better predictor of ESRD than the first ACR.Limitations: The predictive value of ACR measurements is decreased to the extent that its precision is based on a single measure.Conclusion: The predictive power of the latest ACR for ESRD and natural mortality in patients with diabetes is not enhanced by knowledge of the preceding ACR. Therefore, ACR changes over time, ie, regression or progression, add minimal predictive value beyond the latest measurement in the series. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the role of homocysteine as a risk factor for mortality in diabetic subjects. METHODS: Homocysteine, vitamin B(12), and folate concentrations were measured in stored sera of 396 diabetic Pima Indians aged > or = 40 years when examined between 1982 and 1985. Vital status was assessed through 2001. RESULTS AND CONCLUSIONS: Over a median follow-up of 15.7 years, there were 221 deaths-76 were due to cardiovascular disease (CVD), 36 to diabetes/nephropathy and 34 to infections. Homocysteine was positively associated with mortality from all causes (hazard rate ratio (HRR) for highest versus lowest tertile of homocysteine = 1.70, 95% confidence interval (CI) 1.18-2.46), from diabetes/nephropathy (HRR = 2.39, 95% CI 0.94-6.11) and from infectious diseases (HRR = 3.39, 95% CI 1.19-9.70), but not from CVD (HRR = 1.16, 95% CI 0.62-2.17) after adjustment for age, sex and diabetes duration. Homocysteine correlated with serum creatinine (r = 0.50), and the relationships with mortality rates were not significant after adjustment for creatinine. Vitamin B(12) was positively associated with all-cause mortality (HRR for 100 pg/mL difference adjusted for age, sex and diabetes duration = 1.15, 95% CI 1.08-1.22) and death from diabetes/nephropathy (HRR = 1.27, 95% CI 1.10-1.46). The association between homocysteine and mortality in type 2 diabetes is not causal, but is confounded by renal disease in Pima Indians. [ABSTRACT FROM AUTHOR]

Objective: To estimate the global number of excess deaths due to diabetes in the year 2000.Research Design and Methods: We used a computerized generic formal disease model (DisMod II), used by the World Health Organization to assess disease burden through modeling the relationships between incidence, prevalence, and disease-specific mortality. Baseline input data included population structure, age- and sex-specific estimates of diabetes prevalence, and available published estimates of relative risk of death for people with diabetes compared with people without diabetes. The results were validated with population-based observations and independent estimates of relative risk of death.Results: The excess global mortality attributable to diabetes in the year 2000 was estimated to be 2.9 million deaths, equivalent to 5.2% of all deaths. Excess mortality attributable to diabetes accounted for 2-3% of deaths in poorest countries and over 8% in the U.S., Canada, and the Middle East. In people 35-64 years old, 6-27% of deaths were attributable to diabetes.Conclusions: These are the first global estimates of mortality attributable to diabetes. Globally, diabetes is likely to be the fifth leading cause of death. [ABSTRACT FROM AUTHOR]

The combination of insulin resistance, dyslipidemia, hypertension, and obesity has been described as a "metabolic syndrome" that is a strong determinant of type 2 diabetes. Factor analysis was used to identify components of this syndrome in 1,918 Pima Indians. Prospective analyses were conducted to evaluate associations of identified factors with incidence of diabetes. Factor analysis identified 4 factors that accounted for 79% of the variance in the original 10 variables. Each of these factors reflected a proposed component of the metabolic syndrome: insulinemia, body size, blood pressure, and lipid metabolism. Among 890 originally nondiabetic participants with follow-up data, 144 developed diabetes in a median follow-up of 4.1 years. The insulinemia factor was strongly associated with diabetes incidence (incidence rate ratio [IRR] for a 1-SD difference in factor scores = 1.81, P < 0.01). The body size and lipids factors also significantly predicted diabetes (IRR 1.52 and 1.37, respectively, P < 0.01 for both), whereas the blood pressure factor did not (IRR 1.11, P = 0.20). Identification of four unique factors with different associations with incidence of diabetes suggests that the correlations among these variables reflect distinct metabolic processes, about which substantial information may be lost in the attempt to combine them into a single entity. [ABSTRACT FROM AUTHOR]

Lower birth weight is associated with an increased occurrence of type 2 diabetes in later life. Whether this relationship is explained by environmental or genetic factors is unknown. We have examined the potential for genetic influences by determining whether parental diabetes is associated with lower birth weight in 1,608 children of known birth weight and gestational age born between 1941 and 1993 in the Gila River Indian Community in Arizona. The previously described relationships of maternal diabetes to increased birth weight and offspring diabetes were observed. In contrast to this we have determined novel relationships between low birth weight and paternal diabetes. The offspring of diabetic fathers were, on average, 78 g lighter than the offspring of nondiabetic fathers. For fathers, lower birth weight in their offspring was associated with an increased risk of later diabetes, i.e., fathers of offspring in the lowest quintile of birth weight, who were not diabetic at the time of birth of their child, had a 1.8-fold increased risk of developing diabetes later in life (95% CI 1.2-2.7; P = 0.004). For children, lower birth weight predicted diabetes in the offspring if paternal but not maternal diabetes was present, but it was not associated with higher plasma glucose if neither parent had diabetes. We conclude that the risk of diabetes associated with low birth weight is strongly related to the development of paternal diabetes, suggesting a genetic link between lower birth weight and later diabetes. [ABSTRACT FROM AUTHOR]

BACKGROUND: The high prevalence of obesity and type 2 diabetes in some populations is believed to be the expression of a 'thrifty genotype,' which conferred survival advantages during periods of harsh environmental conditions, but has become a liability in industrialized environments of abundance. Low plasma leptin concentrations and a low metabolic rate may be the phenotypic expression of this genotype. OBJECTIVE: We hypothesized that plasma leptin concentrations and resting metabolic rate would be lower in Mexican Pima Indians not yet exposed to an affluent lifestyle than in non-Pima Mexicans living in the same environment. DESIGN: We studied 208 nondiabetic Pima Indians (105 women and 103 men) living a traditional lifestyle in a remote, mountainous area of northwest Mexico and 183 nondiabetic non-Pima Mexicans (90 women and 93 men) living in the same environment. A subset of 40 (17 women and 23 men) Pima Indians and 40 (19 women and 21 men) non-Pima Mexicans was selected for studies of energy metabolism with a ventilated-hood system. RESULTS: Leptin concentrations were strongly correlated with percentage body fat in both groups (r = 0.83, P < 0.0001). There was no significant difference in plasma leptin concentration between groups in absolute value (P = 0.90) or after adjustment for percentage body fat, waist circumference, age, and sex (P = 0.40). Similarly, there was no significant difference in resting metabolic rate between groups in absolute value (P = 0.27) or after adjustment for fat-free mass (P = 0.32). CONCLUSIONS: These results do not support the hypothesis that hypoleptinemia, a relatively low resting metabolic rate, or both are expressions of the thrifty genotype. Copyright (c) 1998 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Abstract Background Preterm birth is a global problem, with a prevalence of 8 to 12% depending on location. Several large trials and systematic reviews have shown progestogens to be effective in preventing or delaying preterm birth in selected high risk women with a singleton pregnancy (including those with a short cervix or previous preterm birth). Although an improvement in short term neonatal outcomes has been shown in some trials these have not consistently been confirmed in meta-analyses. Additionally data on longer term outcomes is limited to a single trial where no difference in outcomes was demonstrated at four years of age of the child, despite those in the “progesterone” group having a lower incidence of preterm birth. Methods/Design The OPPTIMUM study is a double blind randomized placebo controlled trial to determine whether progesterone prophylaxis to prevent preterm birth has long term neonatal or infant benefit. Specifically it will study whether, in women with singleton pregnancy and at high risk of preterm labour, prophylactic vaginal natural progesterone, 200 mg daily from 22 – 34 weeks gestation, compared to placebo, improves obstetric outcome by lengthening pregnancy thus reducing the incidence of preterm delivery (before 34 weeks), improves neonatal outcome by reducing a composite of death and major morbidity, and leads to improved childhood cognitive and neurosensory outcomes at two years of age. Recruitment began in 2009 and is scheduled to close in Spring 2013. As of May 2012, over 800 women had been randomized in 60 sites. Discussion OPPTIMUM will provide further evidence on the effectiveness of vaginal progesterone for prevention of preterm birth and improvement of neonatal outcomes in selected groups of women with singleton pregnancy at high risk of preterm birth. Additionally it will determine whether any reduction in the incidence of preterm birth is accompanied by improved childhood outcome. Trial registration ISRCTN14568373

Abstract Background We determined the diagnostic accuracy of the Edinburgh Claudication Questionnaire (ECQ) in 1st generation Black African-Caribbean UK migrants as previous diagnostic questionnaires have been found to be less accurate in this population. We also determined the diagnostic accuracy of translated versions of the ECQ in 1st generation South Asian UK migrants, as this has not been investigated before. Methods Subjects were recruited from the Ethnic-Echocardiographic Heart of England Screening (E-ECHOES) study, a community based screening survey for heart failure in minority ethnic groups. Translated versions of the ECQ were prepared following a recognised protocol. All participants attending screening between October 2007 and February 2009 were asked to complete the ECQ in the language of their choice (English, Punjabi, Bengali, Urdu, Hindi or Gujarati). Subjects answering positively to experiencing leg pain or discomfort on walking were asked to return to have Ankle Brachial Pressure Index (ABPI) measured. Results 154 out of 2831 subjects participating in E-ECHOES (5.4%) were eligible to participate in this sub-study, for which 74.3% returned for ABPI assessment. Non-responders were younger than participants (59[9] vs. 65[11] years; p = 0.015). Punjabi, English and Bengali questionnaires identified participants with Intermittent Claudication, so these questionnaires were assessed. The sensitivities (SN), specificities (SP), positive (PPV) and negative (NPV) predictive values were calculated. English: SN: 50%; SP: 68%; PPV: 43%; NPV: 74%. Punjabi: SN: 50%; SP: 87%; PPV: 43%; NPV: 90%. Bengali: SN: 33%; SP: 50%; PPV: 13%; NPV: 73%. There were significant differences in diagnostic accuracy between the 3 versions (Punjabi: 83.8%; Bengali: 45%; English: 62.2%; p < 0.0001). No significant differences were found in sensitivity and specificity between illiterate and literate participants in any of the questionnaires and there was no significant different difference between those under and over 60 years of age. Conclusions Our findings suggest that the ECQ is not as sensitive or specific a diagnostic tool in 1st generation Black African-Caribbean and South Asian UK migrants than in the Edinburgh Artery Study, reflecting the findings of other diagnostic questionnaires in these minority ethnic groups. However this study is limited by sample size so conclusions should be interpreted with caution.

Objective: This work aimed to parse out the role of changing environments on body composition, total energy expenditure, and physical activity in the Mexican Pima, a population experiencing rapid industrialization., Methods: Using doubly labeled water, we compared energy expenditure and physical activity in a longitudinal cohort of Mexican Pima (n = 26; female: 12) in 1995 and 2010. Body mass and composition were assessed by bioimpedance analysis. To determine the effects of environmental factors on body weight independent of age, we compared the 1995 longitudinal cohort with an age- and sex-matched cross-sectional cohort (n = 26) in 2010., Results: Body mass, fat mass, and fat-free mass all significantly increased between 1995 and 2010. Despite a 13% average increase in body weight, weight-adjusted total daily energy expenditure decreased significantly. Measured physical activity levels also decreased between 1995 and 2010, after we adjusted for weight., Conclusions: Our results suggest that the recent industrialization of the Maycoba region in Sonora, Mexico, has contributed to a decrease in physical activity, in turn contributing to weight gain and metabolic disease among the Mexican Pima., (© 2024 The Obesity Society.)

Aims: The extent that pre-diabetic fasting plasma glucose (FPG) levels influence the effectiveness of lifestyle interventions in preventing type 2 diabetes (T2DM) is uncertain. We aimed to determine if the outcome of lifestyle intervention in people with impaired glucose tolerance (IGT) differs in those with normal or impaired FPG levels., Materials and Methods: Data were used from the Da Qing Diabetes Prevention Outcome Study, which was a 30-year follow-up of a 6-year randomized trial of lifestyle intervention in 576 people with IGT. We then conducted a post-hoc analysis to compare the efficacy of intervention to reduce the incidence of T2DM and its complications in those with baseline FPG <100 mg/dL and FPG ≥100 mg/dL., Results: Lifestyle intervention reduced the cumulative incidence of T2DM by 37%-46% in those with baseline FPG <100 mg/dL and by 47%-51% in those with FPG ≥100 mg/dL. The FPG <100 mg/dL group had a lower cumulative incidence of diabetes and 6.41 years median delay in its onset compared with 2.21 years delay in the FPG ≥100 mg/dL group. In those with FPG <100 mg/dL intervention was associated with at least as great a reduction in cardiovascular disease and all-cause mortality as in the FPG ≥100 mg/dL group., Conclusions: Lifestyle intervention reduced the incidence of T2DM in people with IGT regardless of baseline FPG levels, and in those with FPG <100 mg/dL led to a substantial delay in its onset. All persons with IGT, with normal or impaired FPG levels, may benefit from lifestyle intervention to delay its onset and mitigate the incidence of T2DM., (© 2021 John Wiley & Sons Ltd.)

Prospective studies in informative populations are crucial to increasing our knowledge of disease. In this perspective, we describe a half century of studies in an American Indian population that transformed our understanding of kidney disease in type 2 diabetes, now recognized as the leading cause of kidney failure worldwide. Serial examinations conducted for many years that included the collection of data and samples across multiple domains captured an unprecedented volume of clinical, physiologic, morphometric, genomic, and transcriptomic data. This work permitted us to extensively characterize the course and determinants of diabetic kidney disease, its pathophysiologic underpinnings, and important secular trends of urgent concern to populations worldwide, including the emergence of youth-onset type 2 diabetes and its effect on development of diabetic kidney disease in midlife. By combining these data using the tools of integrative biology, we are developing new mechanistic insights into the development and progression of diabetic kidney disease in type 2 diabetes. These insights have already contributed to the identification and successful therapeutic targeting of a novel pathway in DKD. We anticipate that this work will continue to expand our understanding of this complex disease and influence its management in the coming years., (© 2021 by the American Diabetes Association.)

Aims/hypothesis: We aimed to determine associations of regression to normal glucose tolerance (NGT), maintaining impaired glucose tolerance (IGT) or progression to diabetes with subsequent risks of CVD and microvascular disease among Chinese adults with IGT., Methods: We conducted an observational study among 540 participants in the Da Qing Diabetes Prevention Study, a 6 year lifestyle intervention trial in people with IGT, defined by 1985 WHO criteria as fasting plasma glucose <7.8 mmol/l and 2 h post-load plasma glucose ≥7.8 and <11.1 mmol/l. At the end of the trial, the groups that had regressed to NGT, remained with IGT or progressed to diabetes were identified. Participants were then followed for 24 years after completion of the trial, during which we compared the incidence and hazard ratios for CVD and microvascular disease in each group and estimated the differences in their median time to onset from parametric Weibull distribution models., Results: At the end of the 6 year trial, 252 (46.7%) participants had developed diabetes, 114 (21.1%) had remained with IGT and 174 (32.2%) had regressed to NGT. Compared with those who developed diabetes during the trial, the median time to onset of diabetes was delayed by 14.86 years (95% CI 12.49, 17.25) in the NGT and 9.87 years (95% CI 8.12, 11.68) in the IGT groups. After completion of the trial, among those with diabetes, IGT and NGT, the 24 year cumulative incidence of CVD was 64.5%, 48.5% and 45.1%, respectively, and 36.8%, 21.7% and 16.5% for microvascular diseases. Compared with participants who had progressed to diabetes during the trial, those who regressed to NGT had a 37% (HR 0.63; 95% CI 0.47, 0.85) reduction in CVD incidence and a median delay of 7.45 years (95% CI 1.91, 12.99) in onset, and those who remained with IGT had a 34% (HR 0.66; 95% CI 0.47, 0.91) lower CVD incidence with a median delay in onset of 5.69 years (95% CI 1.0, 10.38). Participants with NGT had a 66% (HR 0.34; 95% CI 0.20, 0.56) lower incidence of microvascular diseases and a median delay in the onset of 18.66 years (95% CI 6.08, 31.24), and those remaining with IGT had a 52% (HR 0.48; 95% CI 0.29, 0.81) lower incidence with a median delay of 12.56 years (95% CI 2.49, 22.63)., Conclusions/interpretation: People with IGT who reverted to NGT or remained with IGT at the end of the 6 year trial subsequently had significantly lower incidences of CVD and microvascular disease than those who had developed diabetes.

Objective: One-hour plasma glucose (1-h PG) during the oral glucose tolerance test (OGTT) is an accurate predictor of type 2 diabetes. We performed a meta-analysis to determine the optimum cutoff of 1-h PG for detection of type 2 diabetes using 2-h PG as the gold standard., Research Design and Methods: We included 15 studies with 35,551 participants from multiple ethnic groups (53.8% Caucasian) and 2,705 newly detected cases of diabetes based on 2-h PG during OGTT. We excluded cases identified only by elevated fasting plasma glucose and/or HbA 1c . We determined the optimal 1-h PG threshold and its accuracy at this cutoff for detection of diabetes (2-h PG ≥11.1 mmol/L) using a mixed linear effects regression model with different weights to sensitivity/specificity (2/3, 1/2, and 1/3)., Results: Three cutoffs of 1-h PG, at 10.6 mmol/L, 11.6 mmol/L, and 12.5 mmol/L, had sensitivities of 0.95, 0.92, and 0.87 and specificities of 0.86, 0.91, and 0.94 at weights 2/3, 1/2, and 1/3, respectively. The cutoff of 11.6 mmol/L (95% CI 10.6, 12.6) had a sensitivity of 0.92 (0.87, 0.95), specificity of 0.91 (0.88, 0.93), area under the curve 0.939 (95% confidence region for sensitivity at a given specificity: 0.904, 0.946), and a positive predictive value of 45%., Conclusions: The 1-h PG of ≥11.6 mmol/L during OGTT has a good sensitivity and specificity for detecting type 2 diabetes. Prescreening with a diabetes-specific risk calculator to identify high-risk individuals is suggested to decrease the proportion of false-positive cases. Studies including other ethnic groups and assessing complication risk are warranted., (© 2021 by the American Diabetes Association.)

The global epidemic of type 2 diabetes has prompted numerous studies and public health efforts to reduce its development. A variety of interventions, including lifestyle modifications and pharmacological agents directed at ameliorating the major risk factors for type 2 diabetes, are of proven efficacy in reducing the development of type 2 diabetes in people with impaired glucose tolerance. While prevention of the hyperglycaemia characteristic of diabetes is arguably an important, clinically relevant outcome, a more compelling outcome with greater clinical significance is the prevention or reduction of the relatively diabetes-specific microvascular and less-specific cardiovascular disease (CVD) complications associated with diabetes. These complications cause the majority of morbidity and excess mortality associated with diabetes. Any reduction in diabetes should, logically, also reduce the occurrence of its long-term complications; however, most diabetes prevention trials have not been of sufficient duration to allow such an evaluation. The limited long-term data, largely from the Da Qing Diabetes Prevention Study (DQDPS) and the Diabetes Prevention Program (DPP) and their respective follow-up studies (DQDPOS and DPPOS), suggest a reduction in microvascular complications and amelioration of CVD risk factors. Only the DQDPOS and Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) studies have shown a reduction in CVD events and only DQDPOS has demonstrated a decrease in CVD and overall mortality. While these limited data are promising, whether diabetes prevention directly reduces complication-related morbidity and mortality remains unclear. Longer follow-up of prevention studies is needed to supplement the limited current clinical trial data, to help differentiate the effects of diabetes prevention itself from the means used to reduce diabetes development and to understand the balance among benefits, risks and costs of prevention.

Background: Lifestyle interventions can delay the onset of type 2 diabetes in people with impaired glucose tolerance, but whether this leads subsequently to fewer complications or to increased longevity is uncertain. We aimed to assess the long-term effects of lifestyle interventions in people with impaired glucose tolerance on the incidence of diabetes, its complications, and mortality., Methods: The original study was a cluster randomised trial, started in 1986, in which 33 clinics in Da Qing, China, were randomly assigned to either be a control clinic or provide one of three interventions (diet, exercise, or diet plus exercise) for 6 years for 577 adults with impaired glucose tolerance who usually receive their medical care from the clinics. Subsequently, participants were followed for up to 30 years to assess the effects of intervention on the incidence of diabetes, cardiovascular disease events, composite microvascular complications, cardiovascular disease death, all-cause mortality, and life expectancy., Findings: Of the 577 participants, 438 were assigned to an intervention group and 138 to the control group (one refused baseline examination). After 30 years of follow-up, 540 (94%) of 576 participants were assessed for outcomes (135 in the control group, 405 in the intervention group). During the 30-year follow-up, compared with control, the combined intervention group had a median delay in diabetes onset of 3·96 years (95% CI 1·25 to 6·67; p=0·0042), fewer cardiovascular disease events (hazard ratio 0·74, 95% CI 0·59-0·92; p=0·0060), a lower incidence of microvascular complications (0·65, 0·45-0·95; p=0·025), fewer cardiovascular disease deaths (0·67, 0·48-0·94; p=0·022), fewer all-cause deaths (0·74, 0·61-0·89; p=0·0015), and an average increase in life expectancy of 1·44 years (95% CI 0·20-2·68; p=0·023)., Interpretation: Lifestyle intervention in people with impaired glucose tolerance delayed the onset of type 2 diabetes and reduced the incidence of cardiovascular events, microvascular complications, and cardiovascular and all-cause mortality, and increased life expectancy. These findings provide strong justification to continue to implement and expand the use of such interventions to curb the global epidemic of type 2 diabetes and its consequences., Funding: US Centers for Disease Control and Prevention, WHO, Chinese Center for Disease Control and Prevention, World Bank, Ministry of Public Health of the People's Republic of China, Da Qing First Hospital, China-Japan Friendship Hospital, and National Center for Cardiovascular Diseases & Fuwai Hospital., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background and Aim: We sought to determine the effect of regression to normal glucose tolerance (NGT) or progression to diabetes in early years of impaired glucose tolerance (IGT) on subsequent risk of stroke., Methods: In 1986, 576 adults aged 25 years and older with impaired glucose tolerance in Da Qing, China, were randomly assigned by clinic to control, diet, exercise, or diet plus exercise intervention groups for a six-year period. Subsequently participants received medical care in their local clinics. We tracked participants for additional 17 years to ascertain stroke events and other outcomes., Results: At the end of 6-year intervention trial follow-up, 272 (50.2%) had progressed to diabetes, 169 (31.2%) regressed to normal glucose tolerance, and 101 (18.6%) remained impaired glucose tolerance. During the subsequent 17-year follow-up, 173 (31.9%) developed a stroke, 26.7% of normal glucose tolerances, 30.7% of impaired glucose tolerances, and 36.1% of those with diabetes. After controlling for age, sex, baseline blood pressure, smoking, total cholesterol, previous cardiovascular disease and intervention group, those who developed diabetes in the first six years had a higher incidence of stroke than those who reverted to normal glucose tolerance (HR = 1.49, 95% CI 1.01-2.19, p = 0.04), whereas for those who remained impaired glucose tolerance compared to those who regressed to normal glucose tolerance the HR was 1.25 (95% CI 0.80-1.93; p = 0.30). A 1-mmol/L increase in both fasting and 2-h post-load plasma glucose from entry to end of the six-year trial was significantly associated with a higher risk of development of stroke in the subsequent 17 years, respectively (HR = 1.07, 95% CI 1.03-1.11, p < 0.0001 for fasting glucose, HR = 1.05, 95% CI 1.02-1.09, p = 0.007 for 2-h post-load plasma glucose)., Conclusions: Among Chinese adults with impaired glucose tolerance, early progression to diabetes predicted a higher risk of stroke, compared those who regressed to normal glucose tolerance.

Prevalence of diabetes and obesity in Mexican Pima Indians is low, while prevalence in US Pima Indians is high. Although lifestyle likely accounts for much of the difference, the role of genetic factors is not well explored. To examine this, we genotyped 359 single nucleotide polymorphisms, including established type 2 diabetes and obesity variants from genome-wide association studies (GWAS) and 96 random markers, in 342 Mexican Pimas. A multimarker risk score of obesity variants was associated with body mass index (BMI; β = 0.81 kg/m 2 per SD, P = 0.0066). The mean value of the score was lower in Mexican Pimas than in US Pimas (P = 4.3 × 10 -11 ), and differences in allele frequencies at established loci could account for approximately 7% of the population difference in BMI; however, the difference in risk scores was consistent with evolutionary neutrality given genetic distance. To identify loci potentially under recent natural selection, allele frequencies at 283 variants were compared between US and Mexican Pimas, accounting for genetic distance. The largest differences were seen at HLA markers (e.g., rs9271720, difference = 0.75, P = 8.7 × 10 -9 ); genetic distances at HLA were greater than at random markers (P = 1.6 × 10 -46 ). Analyses of GWAS data in 937 US Pimas also showed sharing of alleles identical by descent at HLA that exceeds its genomic expectation (P = 7.0 × 10 -10 ). These results suggest that, in addition to the widely recognized balancing selection at HLA, recent directional selection may also occur, resulting in marked allelic differentiation between closely related populations., (© 2018 John Wiley & Sons Ltd/University College London.)

Background: In Caucasians, lower triglycerides (TG), total or LDL cholesterol and high HDL cholesterol are generally associated with lower mortality. However, low cholesterol is associated with higher mortality in some Asian populations. This study examines the relationship between serum lipids and mortality in American Indians., Methods: 2125 American Indians aged ≥40years were examined biennially between 1993 and 2007. Vital status was determined through 2011. Mortality rates, adjusted for age, sex and diabetes, were calculated using Poisson regression., Results: The median baseline age was 46years and 61% were women. Over a median follow-up of 10.1years, 522 deaths occurred. Relationships between baseline lipids, except for HDL cholesterol, and all-cause mortality were negative and linear in persons without diabetes and U-shaped in persons with diabetes. For HDL cholesterol, the relationship was U-shaped in the total cohort. Cardiovascular mortality was positively associated with total, LDL and non-HDL cholesterol whereas lower lipid concentrations were adversely associated with mortality from liver disease or external causes, except for HDL cholesterol, where associations were positive., Conclusion: The common belief that low cholesterol and TG are beneficial for health is not universally observed; evidence suggests increased mortality at both ends of the cholesterol and TG distributions., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To determine whether early administration of losartan slows progression of diabetic kidney disease over an extended period., Research Design and Methods: We conducted a 6-year clinical trial in 169 American Indians with type 2 diabetes and urine albumin/creatinine ratio <300 mg/g; 84 participants were randomly assigned to receive losartan and 85 to placebo. Primary outcome was a decline in glomerular filtration rate (GFR; iothalamate) to ≤60 mL/min or to half the baseline value in persons who entered with GFR <120 mL/min. At enrollment, GFR averaged 165 mL/min (interquartile range 49-313 mL/min). During the trial, nine persons reached the primary outcome with a hazard ratio (HR; losartan vs. placebo) of 0.50 (95% CI 0.12-1.99). Participants were then followed posttrial for up to 12 years, with treatment managed outside the study. The effect of losartan on the primary GFR outcome was then reanalyzed for the entire study period, including the clinical trial and posttrial follow-up., Results: After completion of the clinical trial, treatment with renin-angiotensin system inhibitors was equivalent in both groups. During a median of 13.5 years following randomization, 29 participants originally assigned to losartan and 35 to placebo reached the primary GFR outcome with an HR of 0.72 (95% CI 0.44-1.18)., Conclusions: Long-term risk of GFR decline was not significantly different between persons randomized to early treatment with losartan and those randomized to placebo. Accordingly, we found no evidence of an extended benefit of early losartan treatment on slowing GFR decline in persons with type 2 diabetes., (© 2016 by the American Diabetes Association.)

Diabetes mellitus is one of the most important public health challenges of the twenty-first century. Until the past decade, it has been seriously underrated as a global health threat. Major gaps exist in efforts to comprehend the burden nationally and globally, especially in developing nations, due to a lack of accurate data for monitoring and surveillance. Early attempts to obtain accurate data, discussed in this article, seem to have been cast aside so, at present, these needs remain unmet. Existing international efforts to assemble information fall far short of requirements. Current estimates are imprecise, only providing a rough picture, and probably underestimate the disease burden. The methodologies that are currently used, and that are discussed in this Perspectives article, are inadequate for providing a complete and accurate assessment of the prevalence of diabetes mellitus. International consensus on uniform standards and criteria for reporting national data on diabetes mellitus prevalence as well as for common complications of diabetes mellitus and mortality need to be developed.

Objective: People with impaired glucose tolerance (IGT) have increased risk of mortality and a high risk of progression to diabetes, but the extent that the excess mortality is associated with IGT per se or is the result of subsequent diabetes is unclear., Research Design and Methods: We compared mortality before and after the development of diabetes among 542 persons with IGT initially who participated in a 6-year lifestyle diabetes prevention trial and were followed-up from 1986 to 2009., Results: During the 23-year follow-up, 174 (32.1%) died, with an overall death rate of 15.9/1,000 person-years. The majority of deaths (74.7%; 130 of 174) occurred after progression to type 2 diabetes, with age-adjusted death rates of 11.1/1,000 person-years (95% CI 8.2-12.0) before and 19.4/1,000 person-years (95% CI 11.9-23.3) after the development of type 2 diabetes. The cumulative mortality was 37.8% (95% CI 33.1-42.2%) in participants who developed type 2 diabetes during first 10 years of follow-up, 28.6% (95% CI 21.6-35.0%) in those who progressed to type 2 diabetes in 10-20 years, and 13.9% (95% CI 7.0-20.3%) in those who did not develop to type 2 diabetes within 20 years. Time-dependent multivariate Cox proportional hazards analyses, with adjustment for baseline age, sex, intervention, and other potential confounding risk factors, showed that the development of type 2 diabetes was associated with a 73% higher risk of death (hazard ratio 1.73 [95% CI 1.18-2.52])., Conclusions: As elsewhere, IGT is associated with increased risk of mortality in China, but much of this excess risk is attributable to the development of type 2 diabetes., (© 2016 by the American Diabetes Association.)