Peter H. Bennett

Effects of Diet and Exercise in Preventing NIDDM in People With Impaired Glucose Tolerance: The Da Qing IGT and Diabetes Study

OBJECTIVE Individuals with impaired glucose tolerance (IGT) have a high risk of developing NIDDM. The purpose of this study was to determine whether diet and exercise interventions in those with IGT may delay the development of NIDDM, i.e., reduce the incidence of NIDDM, and thereby reduce the overall incidence of diabetic complications, such as cardiovascular, renal, and retinal disease, and the excess mortality attributable to these complications. RESEARCH DESIGN AND METHODS In 1986, 110,660 men and women from 33 health care clinics in the city of Da Qing, China, were screened for IGT and NIDDM. Of these individuals, 577 were classified (using World Health Organization criteria) as having IGT. Subjects were randomized by clinic into a clinical trial, either to a control group or to one of three active treatment groups: diet only, exercise only, or diet plus exercise. Follow-up evaluation examinations were conducted at 2-year intervals over a 6-year period to identify subjects who developed NIDDM. Coxs proportional hazard analysis was used to determine if the incidence of NIDDM varied by treatment assignment. RESULTS The cumulative incidence of diabetes at 6 years was 67.7% (95% CI, 59.8–75.2) in the control group compared with 43.8% (95% CI, 35.5–52.3) in the diet group, 41.1% (95% CI, 33.4–49.4) in the exercise group, and 46.0% (95% CI, 37.3–54.7) in the diet-plus-exercise group (P < 0.05). When analyzed by clinic, each of the active intervention groups differed significantly from the control clinics (P < 0.05). The relative decrease in rate of development of diabetes in the active treatment groups was similar when subjects were stratified as lean or overweight (BMI < or ≥ 25 kg/m2). In a proportional hazards analysis adjusted for differences in baseline BMI and fasting glucose, the diet, exercise, and diet-plus-exercise interventions were associated with 31% (P < 0.03), 46% (P < 0.0005), and 42% (P < 0.005) reductions in risk of developing diabetes, respectively. CONCLUSIONS Diet and/or exercise interventions led to a significant decrease in the incidence of diabetes over a 6-year period among those with IGT.

Diabetes mellitus statistics on prevalence and mortality: facts and fallacies

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.

Insulin Resistance and Insulin Secretory Dysfunction as Precursors of Non-Insulin-Dependent Diabetes Mellitus: Prospective Studies of Pima Indians

BACKGROUND The relative roles of obesity, insulin resistance, insulin secretory dysfunction, and excess hepatic glucose production in the development of non-insulin-dependent diabetes mellitus (NIDDM) are controversial. We conducted a prospective study to determine which of these factors predicted the development of the disease in a group of Pima Indians. METHODS A body-composition assessment, oral and intravenous glucose-tolerance tests, and a hyperinsulinemic--euglycemic clamp study were performed in 200 non-diabetic Pima Indians (87 women and 113 men; mean [+/- SD] age, 26 +/- 6 years). The subjects were followed yearly thereafter for an average of 5.3 years. RESULTS Diabetes developed in 38 subjects during follow-up. Obesity, insulin resistance (independent of obesity), and low acute plasma insulin response to intravenous glucose (with the degree of obesity and insulin resistance taken into account) were predictors of NIDDM: The six-year cumulative incidence of NIDDM was 39 percent in persons with values below the median for both insulin action and acute insulin response, 27 percent in those with values below the median for insulin action but above that for acute insulin response, 13 percent in those with values above the median for insulin action and below that for acute insulin response, and 0 in those with values originally above the median for both characteristics. CONCLUSIONS Insulin resistance is a major risk factor for the development of NIDDM: A low acute insulin response to glucose is an additional but weaker risk factor.

The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study.

BACKGROUND Intensive lifestyle interventions can reduce the incidence of type 2 diabetes in people with impaired glucose tolerance, but how long these benefits extend beyond the period of active intervention, and whether such interventions reduce the risk of cardiovascular disease (CVD) and mortality, is unclear. We aimed to assess whether intensive lifestyle interventions have a long-term effect on the risk of diabetes, diabetes-related macrovascular and microvascular complications, and mortality. METHODS In 1986, 577 adults with impaired glucose tolerance from 33 clinics in China were randomly assigned to either the control group or to one of three lifestyle intervention groups (diet, exercise, or diet plus exercise). Active intervention took place over 6 years until 1992. In 2006, study participants were followed-up to assess the long-term effect of the interventions. The primary outcomes were diabetes incidence, CVD incidence and mortality, and all-cause mortality. FINDINGS Compared with control participants, those in the combined lifestyle intervention groups had a 51% lower incidence of diabetes (hazard rate ratio [HRR] 0.49; 95% CI 0.33-0.73) during the active intervention period and a 43% lower incidence (0.57; 0.41-0.81) over the 20 year period, controlled for age and clustering by clinic. The average annual incidence of diabetes was 7% for intervention participants versus 11% in control participants, with 20-year cumulative incidence of 80% in the intervention groups and 93% in the control group. Participants in the intervention group spent an average of 3.6 fewer years with diabetes than those in the control group. There was no significant difference between the intervention and control groups in the rate of first CVD events (HRR 0.98; 95% CI 0.71-1.37), CVD mortality (0.83; 0.48-1.40), and all-cause mortality (0.96; 0.65-1.41), but our study had limited statistical power to detect differences for these outcomes. INTERPRETATION Group-based lifestyle interventions over 6 years can prevent or delay diabetes for up to 14 years after the active intervention. However, whether lifestyle intervention also leads to reduced CVD and mortality remains unclear.

Prevalence of Diabetes and Impaired Glucose Tolerance and Plasma Glucose Levels in U.S. Population Aged 20–74 Yr

The prevalence of physician-diagnosed diabetes and of undiagnosed diabetes and impaired glucose tolerance (IGT) that meet National Diabetes Data Group (NDDG) and World Health Organization (WHO) criteria have been estimated for the U.S. population aged 20–74 yr from the 1976–1980 National Health and Nutrition Examination Survey. This survey included a demographic/medical history questionnaire administered in the participants home and a detailed examination composed of a physicians exam, special clinical procedures, other tests, and collection of blood and urine specimens. Survey participants were selected from 1970 census data through a stratified multistage probability sampling scheme. Of 17,390 eligible residents aged 20–74 yr, 15,357 (88.3%) participated in the interview and are the basis for estimates of diagnosed diabetes; 11,858 (68%) participated in the exam. A half sample of 5901 examinees was selected to receive a 75-g oral glucose tolerance test (OGTT) performed in the morning after an overnight 10- to 16-h fast. Of these examinees, valid OGTT data were obtained for 3772 people without a medical history of diabetes, and these are the basis for estimates of undiagnosed diabetes and IGT. The major reasons for incomplete OGTT data were inability of participants to attend the examination center in the morning and lack of adherence to the fasting instructions. Despite the relatively low response rates, evidence is presented that data on both the interviewed sample and those receiving the OGTT, when adjusted for the 1970–1980 census characteristics by age, race, sex, income, and geographic location, are representative of the U.S. population. Extrapolation of these data to the U.S. population aged 20–74 yr indicates a total diabetes prevalence of 6.6% by NDDG criteria, or more than 8 million people with diabetes. The prevalence of undiagnosed diabetes (3.2%) was almost equal to that of previously diagnosed diabetes (3.4%). Total rates of diabetes increased with age, from 2.0% at age 20–44 yr to 17.7% at age 65–74 yr. Rates were approximately equal by sex but were greater in Blacks than in Whites. The prevalence of undiagnosed diabetes by WHO criteria (3.4%) was similar to that by NDDG criteria, but the rate of impaired glucose tolerance (11.2%) was more than twice the NDDG estimate (4.6%). Both obesity and parental history of diabetes were associated with significantly higher rates of diabetes and IGT. Fasting plasma glucose was relatively insensitive to age, but 1-h and 2-h post-75-g glucose values increased significantly with age.

THE METABOLIC SYNDROME IN CHILDREN AND ADOLESCENTS – AN IDF CONSENSUS REPORT

Zimmet P, Alberti K George MM, Kaufman F, Tajima N, Silink M, Arslanian S, Wong G, Bennett P, Shaw J, Caprio S; IDF Consensus Group. The metabolic syndrome in children and adolescents – an IDF consensus report. Pediatric Diabetes 2007: 8: 299–306. Paul Zimmet, K George MM Alberti, Francine Kaufman, Naoko Tajima, Martin Silink, Silva Arslanian, Gary Wong, Peter Bennett, Jonathan Shaw and Sonia Caprio; IDF Consensus Group International Diabetes Institute, Melbourne, Victoria, Australia; Department of Endocrinology and Metabolic Medicine, St Mary’s Hospital, London, UK; Center for Diabetes, Endocrinology and Metabolism, Children’s Hospital, Los Angeles, CA, USA; Division of Diabetes, Metabolism and Endocrinology, Jikei University School of Medicine, Tokyo, Japan; Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Sydney, New South Wales, Australia; Division of Endocrinology, Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA; Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong; Phoenix Epidemiology and Clinical Research Branch, NIDDK, National Institutes of Health, Phoenix, AZ, USA; and Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA

The metabolic syndrome in children and adolescents

www.thelancet.com Vol 369 June 23, 2007 2059 and community mobilisation was possible for the Mitanin programme, but there were no community-level baselines or controls in the programme design to measure outcomes, and suffi cient sample sizes were neither easy nor aff ordable. At this stage, outcomes can be assessed only by use of indicators in independent surveys of national health and demographics. These surveys show that the rural infant mortality in Chhattisgarh decreased from 85 deaths per 1000 livebirths in 2002 to 65 deaths per 1000 livebirths in 2005, which is much the same as the national rural infant mortality rate (64 deaths per 1000 livebirths). However, estimation of the precise contribution of the Mitanin programme to this decrease is diffi cult. Much of the improvement in child survival in Chhattisgarh undoubtedly relates to better healthseeking behaviour and child-care practices. The initiation of breastfeeding in the fi rst 2 h after birth increased from 24% of livebirths to 71% of livebirths, and the use of oral rehydration salts in the management of diarrhoea in children younger than 3 years increased by 12% in the 2 weeks before the survey. These two interventions substantially aff ect child survival, and were highly mon i tored and eff ective Mitanin interventions. Other re corded improvements include total immunisation and ante natal care, to which Mitanins would have lent support. Community participation and the empowerment of women cause change. The many Mitanins who have since entered elected offi ce in local governance bodies, and the successful Mitanin-led community actions against deforestation, for securing of tribal liveli hoods, for early childhood-care facilities, or against alcoholism and corruption are testimonies to the so-called unintend ed positive outcomes. However, as the programme grows, these actions will pose new problems for the sus tainability of large-scale CHW programmes, and might again lay bare the tensions between the diff erent expec tations and descriptions of the CHW.

Birth weight and non-insulin dependent diabetes : Thrifty genotype, thrifty phenotype, or surviving small baby genotype?

Abstract Objective : To determine the prevalence of diabetes in relation to birth weight in Pima Indians. Design : Follow up study of infants born during 1940-72 who had undergone a glucose tolerance test at ages 20-39 years. Setting : Gila River Indian community, Arizona. Subjects : 1179 American Indians. Main outcome measure: Prevalence of non-insulin dependent diabetes mellitus (plasma glucose concentration >=11.1 mmol/l two hours after ingestion of carbohydrate). Results : The prevalence was greatest in those with the lowest and highest birth weights. The age adjusted prevalences for birth weights <2500 g, 2500-4499 g, and >=4500 g were 30%, 17%, and 32%, respectively. When age, sex, body mass index, maternal diabetes during pregnancy, and birth year were controlled for, subjects with birth weights <2500 g had a higher rate than those with weights 2500-4499 g (odds ratio 3.81; 95% confidence interval 1.70 to 8.52). The risk for subsequent diabetes among higher birthweight infants (>=4500 g) was associated with maternal diabetes during pregnancy. Most diabetes, however, occurred in subjects with intermediate birth weights (2500-4500 g). Conclusions : The relation of the prevalence of diabetes to birth weight in the Pima Indians is U shaped and is related to parental diabetes. Low birth weight is associated with non-insulin dependent diabetes. Given the high mortality of low birthweight infants selective survival in infancy of those genetically predisposed to insulin resistance and diabetes provides an explanation for the observed relation between low birth weight and diabetes and the high prevalence of diabetes in many populations.

Development of Questionnaire to Examine Relationship of Physical Activity and Diabetes in Pima Indians

There was a need to design a questionnaire that could accurately assess the activity patterns of Native Americans to evaluate the relationship between physical activity and diabetes. Such a questionnaire was developed and implemented into the data collection scheme of the prospective Pima Indian Study of Arizona. The questionnaire, which assesses historical, past-year, and past-week leisure and occupational activity, was examined in 29 Pima individuals aged 21–36 yr and was shown to be reliable with test-retest correlations (rank-order correlations ranged from 0.62 to 0.96 for leisure and occupational activity). Reproducibility of the past-year leisure physical-activity estimate was determined in 69 participants aged 10-59 yr and was found to be reliable in all age-groups with the exception of the 10- to 14-yr-old age-group (rank-order correlations were 0.31 in the 10- to 14-yr-old age-group compared to 0.88 to 0.92 in those >20 yr of age). Validity of the current-activity section of the questionnaire was demonstrated indirectly through comparisons with activity monitors. The past-week leisure-activity estimate was related to the Caltrac activity monitor counts per hour (p = 0.62, P > 0.05, n = 17). In summary, a physical-activity questionnaire has been developed that is both reliable and feasible to use in the Pima Indian population to evaluate the relationship of physical activity to non-insulin-dependent diabetes mellitus.

Impaired glucose tolerance as a disorder of insulin action. Longitudinal and cross-sectional studies in Pima Indians.

Impaired glucose tolerance often presages the development of non-insulin-dependent diabetes mellitus. We have studied insulin action and secretion in 24 Pima Indians before and after the development of impaired glucose tolerance and in 254 other subjects representing the whole spectrum of glucose tolerance, including subjects with overt non-insulin-dependent diabetes. The transition from normal to impaired glucose tolerance was associated with a decrease in glucose uptake during hyperinsulinemia, from 0.018 to 0.016 mmol per minute (from 3.3 to 2.8 mg per kilogram of fat-free body mass per minute) (P less than 0.0003). Mean plasma insulin concentrations increased during an oral glucose-tolerance test, from 1200 to 1770 pmol per liter (from 167 to 247 microU per milliliter). In 151 subjects with normal glucose tolerance, the insulin concentration measured during an oral glucose-tolerance test correlated with the plasma glucose concentration (r = 0.48, P less than or equal to 0.0001). This relation was used to predict an insulin concentration of 1550 pmol per liter (216 microU per milliliter) in subjects with impaired glucose tolerance (actual value, 1590 pmol per liter [222 microU per milliliter]; P not significant), suggesting that these subjects had normal secretion of insulin. In contrast, plasma insulin concentrations in the diabetics decreased as glucose concentrations increased (r = -0.75, P less than or equal to 0.0001), suggesting deficient secretion of insulin. This relative insulin deficiency first appears at the lower end of the second (diabetic) mode seen in population frequency distributions of plasma glucose concentrations. Our data show that impaired glucose tolerance in our study population is primarily due to impaired insulin action. In patients with non-insulin-dependent diabetes mellitus, by contrast, impaired insulin action and insulin secretory failure are both present.