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Biomedical subjects

D J Pettitt

Publications and source records attributed to D J Pettitt.

At least 19 recordsLinked to original sources
PubMed2006

Pregnancy plasma glucose levels exceeding the American Diabetes Association thresholds, but below the National Diabetes Data Group thresholds for gestational diabetes mellitus, are related to the risk of neonatal macrosomia, hypoglycaemia and hyperbilirubinaemia.

AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is a risk factor for perinatal complications. In several countries, the criteria for the diagnosis of GDM have been in flux, the American Diabetes Association (ADA) thresholds recommended in 2000 being lower than those of the National Diabetes Data Group (NDDG) that have been in use since 1979. We sought to determine the extent to which infants of women meeting only the ADA criteria for GDM are at increased risk of neonatal complications. MATERIALS AND METHODS: In a multiethnic cohort of 45,245 women who did not meet the NDDG criteria and were not treated for GDM, we conducted nested case-control studies of three complications of GDM that occurred in their infants: macrosomia (birthweight >4,500 g, n = 494); hypoglycaemia (plasma glucose <2.2 mmo/l, n = 488); and hyperbilirubinaemia (serum bilirubin > or =342 micromol/l (20 mg/dl), n = 578). We compared prenatal glucose levels of the mothers of these infants and mothers of 884 control infants. RESULTS: Women with GDM by ADA criteria only (two or more glucose values exceeding the threshold) had an increased risk of having an infant with macrosomia (odds ratio OR = 3.40, 95% CI = 1.55-7.43), hypoglycaemia (OR = 2.61, 95% CI = 0.99-6.92) or hyperbilirubinaemia (OR = 2.22, 95% CI = 0.98-5.04). Glucose levels 1 h after the 100-g glucose challenge that exceeded the ADA threshold were particularly strongly associated with each complication. CONCLUSIONS/INTERPRETATION: These results lend support to the ADA recommendations and highlight the importance of the 1-h glucose measurement in a diagnostic test for GDM.

Blood Glucose↗
PubMed2004

The combination oral and nutritional treatment of late-onset diabetes mellitus (CONTROL DM) trial results.

OBJECTIVE: To examine the effect of short-term improvements in glycaemic control on brachial artery endothelial function as a marker of cardiovascular health. METHODS: Persons with Type 2 diabetes who were poorly controlled on oral therapy were randomly assigned to monotherapy with repaglinide or combination therapy with repaglinide plus metformin. Brachial artery flow-mediated vasodilation was assessed by ultrasonography at randomization and following 16 weeks of therapy. The primary outcome was change in brachial artery endothelial function from baseline. Comparison of randomized groups was a secondary aim. RESULTS: Eighty-six participants were randomized, and 83 were followed to study completion. Post occlusion brachial artery vasodilation was 3.74% at baseline and 3.82% following 16 weeks of therapy (P = 0.77). The treatment effect was 0.08% (95% CI: -0.48%, 0.64%). No difference was seen between treatment groups (P = 0.69). Overall, A1C was reduced from 8.3% to 7.0%, with a greater reduction in the combination therapy group (from 8.4% to 6.7%) than in the monotherapy group (from 8.3% to 7.3%, p for difference between groups = 0.01). Statistically significant reductions were observed in fasting glucose, and plasminogen activator inhibitor-1. Statistically significant increases were observed for fasting insulin, uric acid, weight and BMI. CONCLUSIONS: Brachial artery endothelial function was not influenced by short-term improvements in glycaemic control. The CONTROL DM group was successful in lowering A1C. Future research should explore more intensive and longer-lasting improvements in glycaemic control on endothelial function. Some data previously published in abstract form (Diabetes 2001; 50 (Suppl. 2): A217).

Administration, Oral↗
PubMed2001

Joint swelling as a predictor of death from cardiovascular disease in a population study of Pima Indians.

OBJECTIVE: Markers of inflammation have recently been shown to be predictive of cardiovascular disease (CVD). Furthermore, the excess mortality in rheumatoid arthritis (RA), a disease characterized by chronic polyarthritis, is chiefly due to death from CVD. With this background, we studied the effect of inflammation, as reflected by the number of joints with soft tissue swelling, and rheumatoid factor (RF) seropositivity on CVD-related mortality. METHODS: Mortality rates and rate ratios for all-cause and CVD-related deaths were computed in a longitudinal, population-based cohort of Pima Indians in Arizona from 1965 through 1994. Repeated health examinations were performed, involving systematic assessment of the features of RA, cardiovascular risk factors, serum titers of RF, as well as mortality. The cohort comprised 4,120 subjects (1,861 men, 2,259 women) who were examined an average of 3.5 times during a mean followup of 14 years. RESULTS: During the followup period, 182 CVD-related deaths ocurred. The age- and sex-adjusted CVD-related mortality rates increased significantly with the presence of a higher number of joints with soft tissue swelling (Ptrend = 0.04), and were 2.07 (95% confidence interval [95% CI] 1.30-3.31) times as high in those subjects who had 2 or more swollen joints as in those who had none. There were no significant additional effects on CVD-related mortality when seropositivity for RF or a previous diagnosis of RA were considered. In age- and sex-adjusted proportional hazards analyses, which were controlled for possible confounders, the effect of swollen joints remained significant (mortality rate ratio 1.33, 95% CI 1.04-1.71 per category increase [no swollen joints, 1 swollen joint, at least 2 swollen joints]). CONCLUSION: Joint swelling is a significant risk factor for CVD-related death, independent of other known risk factors including a diagnosis of RA. This finding supports the hypothesis that inflammatory mechanisms are important for the development of CVD.

Adult↗
PubMed2001

Birth weight as a predictor of type 2 diabetes mellitus: the U-shaped curve.

Recent findings have sparked intense interest in birth weight as a predictor of type 2 diabetes mellitus. In some populations, there is an inverse association between birth size and disease; however, in the Pima Indians, a population with very high rates of gestational diabetes, high birth weight and low birth weight are associated with diabetes. This results in a U-shaped curve with higher diabetes rates in both tails of the distribution. Similarly, there are reports of an inverse association between stature and prevalence of gestational diabetes, but, in California Latina women with gestational diabetes, there is a positive association between stature and glucose concentration. Could these disparate findings also represent the two ends of a U-shaped curve? The disparities are likely due to differences in the environment, both in utero and postnatally, that different groups experience.

Adult↗
PubMed2000

Evaluation of simple indices of insulin sensitivity and insulin secretion for use in epidemiologic studies.

The metabolic characteristics of type 2 diabetes, insulin resistance, and diminished insulin secretion are costly to measure directly. To evaluate the utility of several simple indices derived from insulin and glucose measurements, the indices were examined from 1982 to 1997 with respect to correlation with more sophisticated measures of insulin sensitivity and secretion in Pima Indians in the Gila River Indian Community of Arizona. Ability to predict the incidence of diabetes in 1,731 persons was also examined. Indices were calculated from fasting and 2-hour glucose (G0, G120) and insulin (I0, I120) concentrations obtained during an oral glucose tolerance test. Fasting serum insulin concentration and the insulin sensitivity index (10(4)/(I0 x G0)) each showed a moderate correlation with the estimate of insulin sensitivity derived from the hyperinsulinemic-euglycemic clamp (absolute value r approximately 0.60). They also strongly predicted the incidence of diabetes (incidence rate ratio comparing the most and least insulin-resistant tertile groups approximately 3.0). Corrected insulin response (I120/(G120 x (G120 - 70))) was modestly correlated with insulin secretion as measured by an intravenous glucose tolerance test (r = 0.35). Impaired insulin secretion assessed by this index predicted incidence of diabetes, particularly after control for insulin sensitivity index (incidence rate ratio = 1.6). Thus, simple indices of insulin sensitivity and secretion may be reasonable surrogates for more sophisticated measures in epidemiologic studies.

Adult↗
PubMed2000

Type 2 diabetes among North American children and adolescents: an epidemiologic review and a public health perspective.

OBJECTIVES: To review the magnitude, characteristics, and public health importance of type 2 diabetes in North American youth. RESULTS: Among 15- to 19-year-old North American Indians, prevalence of type 2 diabetes per 1000 was 50.9 for Pima Indians, 4.5 for all US American Indians, and 2.3 for Canadian Cree and Ojibway Indians in Manitoba. From 1967-1976 to 1987-1996, prevalence increased 6-fold for Pima Indian adolescents. Among African Americans and whites aged 10 to 19 years in Ohio, type 2 diabetes accounted for 33% of all cases of diabetes. Youth with type 2 diabetes were generally 10 to 19 years old, were obese and had a family history of type 2 diabetes, had acanthosis nigricans, belonged to minority populations, and were more likely to be girls than boys. At follow-up, glucose control was often poor, and diabetic complications could occur early. CONCLUSIONS: Type 2 diabetes is an important problem among American Indian and First Nation youth. Other populations have not been well studied, but cases are now occurring in all population groups, especially in ethnic minorities. Type 2 diabetes among youth is an emerging public health problem, for which there is a great potential to improve primary and secondary prevention.

Adolescent↗
PubMed2000

A locus influencing total serum cholesterol on chromosome 19p: results from an autosomal genomic scan of serum lipid concentrations in Pima Indians.

A genome-wide linkage study was analyzed to identify loci that influence serum lipid concentrations in Pima Indians. Linkage analyses were conducted for total cholesterol measured in 998 siblings from 292 nuclear families, for total triglycerides in 547 siblings from 188 families, and for high density lipoprotein (HDL) cholesterol in 590 siblings from 201 families. Genotypes were generated for 516 autosomal microsatellite markers. Multipoint variance components methods were used to assess linkage. The strongest evidence for linkage with total cholesterol was on chromosome 19p (lod score 3.89), in the vicinity of the marker D19S1034, which is near the low density lipoprotein receptor gene. The strongest evidence for linkage with HDL cholesterol was on chromosome 3q (lod score 2.64) near D3S3053. For triglycerides, the strongest evidence for linkage was on chromosome 2p near D2S1788 (lod score 1.70) and on chromosome 3p near D3S2406 (lod score 1.77). This genomic scan provides evidence for a locus influencing total cholesterol concentration on chromosome 19p. It also suggests a locus influencing HDL cholesterol on chromosome 3q.

Adult↗
PubMed2000

Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships.

Intrauterine exposure to diabetes is associated with an excess of diabetes and obesity in the offspring, but the effects of intrauterine exposure are confounded by genetic factors. To determine the role of the intrauterine diabetic environment per se, the prevalence of diabetes and the mean BMI were compared in siblings born before and after their mother was recognized as having diabetes. Nuclear families in which at least one sibling was born before and one after the mother was diagnosed with type 2 diabetes were selected. Consequently, the siblings born before and after differed in their exposure to diabetes in utero. A total of 58 siblings from 19 families in which at least one sibling had diabetes were examined at similar ages (within 3 years). The risk of diabetes was significantly higher in siblings born after the mother developed diabetes than in those born before the mother's diagnosis of diabetes (odds ratio 3.7, P = 0.02). In 52 families, among 183 siblings without diabetes, the mean BMI was 2.6 kg/m2 higher in offspring of diabetic than in offspring of nondiabetic pregnancies (P = 0.003). In contrast, there were no significant differences in risk of diabetes or BMI between offspring born before and after the father was diagnosed with diabetes. Intrauterine exposure to diabetes per se conveys a high risk for the development of diabetes and obesity in offspring in excess of risk attributable to genetic factors alone.

Adult↗
PubMed2000

Segregation analysis of diabetic nephropathy in Pima Indians.

Familial aggregation of diabetic nephropathy suggests the existence of genes determining susceptibility to nephropathy in addition to those leading to diabetes. In the present study, complex segregation analysis was performed in diabetic members of Pima Indian families to determine whether familial aggregation of nephropathy in this population could reflect the action of a single major gene. Nephropathy, defined by a urinary protein-to-creatinine ratio (PCR) > or = 500 mg/g, was analyzed as a discrete trait in a class C regressive logistic model. Individuals with PCR <500 mg/g were considered unaffected. Segregation analysis was performed both for nephropathy at the last examination (prevalent cases) and for duration of diabetes at the onset of nephropathy (incident cases). The REGD program was used for the analysis of the prevalent cases and the REGTL program for the incident cases, both from the Statistical Analysis for Genetic Epidemiology package (Case Western University, Cleveland, OH). The analysis of prevalent cases included 2,107 Pima Indians from 715 nuclear families. A subset of 504 of these families containing 1,403 individuals was used in the analysis of incident cases. Analysis of prevalent cases supported the existence of a gene with a major role, in that hypotheses of no major effect and of no transmission of a major effect were rejected (P = 0.00001; P = 0.003), whereas Mendelian transmission was not rejected (P = 0.85). A dominant model provided the best fit, but a recessive model could not be rejected. The analysis of incident cases, however, did not support a major gene effect on duration of diabetes at the onset of nephropathy, and analyses of lifetime occurrence of nephropathy were inconclusive. The analysis of prevalent cases supports the hypothesis of a major genetic effect on susceptibility to diabetic nephropathy in Pima Indians, but the analysis of incident cases does not support a genetic effect on duration of diabetes at the onset of nephropathy. The discrepancy may reflect the difficulty in precisely dating onset of nephropathy. The parameters of the model derived from segregation analysis of prevalent cases may be useful in linkage studies to detect nephropathy susceptibility loci.

Adult↗
PubMed1999

Type 2 diabetes mellitus in minority children and adolescents. An emerging problem.

Type 2 diabetes mellitus is a disease of adults and has been considered rare in the pediatric population. Over the last decade, however, there has been a disturbing trend of increasing cases of type 2 diabetes in children, particularly adolescents, and with a greater proportion of minority children being affected. This article reviews the clinical characteristics of youth with type 2 diabetes, presents the risk factors associated with insulin resistance and type 2 diabetes, discusses treatment options, and projects future directions in research. The ultimate goal is to raise awareness of this challenging entity among healthcare professionals.

Adolescent↗
PubMed1999

Comparison of the effect of saturated and monounsaturated fat on postprandial plasma glucose and insulin concentration in women with gestational diabetes mellitus.

The goal of this study was to determine whether the type of fat plays a role in the glucose response to a meal, independent of the carbohydrate content. Ten gestational diabetic women (gestational weeks 29-34) who were well controlled on diet alone were randomized as to the order in which they would eat a meal, after overnight fast, containing saturated fat (SF) or monounsaturated fat (MUFA). Blood was drawn at 0, 60, 120, and 180 min for plasma glucose, insulin, lipid profile (triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol) and free fatty acids. After 2 weeks, each patient received the other type of meal. The test meal was composed of 20% of the total daily caloric needs based on ideal body weight. The area under the curve showed a significantly lower glucose concentration for SF meal (p = 0.001). Serum insulin concentrations followed the glucose response with the peak at the 60-min time point and a significantly lower concentration at the 180-min time point in the SF than in the MUFA group. The present study demonstrated that the addition of SF to the meal resulted in lower postprandial glucose and insulin than when the meal contained MUFA. Thus, SF may be useful in controlling postprandial glucose.

Adult↗
PubMed1999

Birth weight, type 2 diabetes, and insulin resistance in Pima Indian children and young adults.

OBJECTIVE: To investigate the mechanisms underlying the association between birth weight and type 2 diabetes in a population-based study of 3,061 Pima Indians aged 5-29 years. RESEARCH DESIGN AND METHODS: Glucose and insulin concentrations were measured during a 75-g oral glucose tolerance test, and insulin resistance was estimated according to the homeostatic model (homeostasis model assessment-insulin resistance [HOMA-IR]). Relationships between birth weight, height, weight, fasting and postload concentrations of glucose and insulin, and HOMA-IR were examined with multiple regression analyses. RESULTS: Birth weight was positively related to current weight and height (P < 0.0001, controlled for age and sex, in each age-group). The 2-h glucose concentrations showed a U-shaped relationship with birth weight in subjects > 10 years of age, and this relation was independent of current body size. In 2,272 nondiabetic subjects, after adjustment for weight and height, fasting and 2-h insulin concentrations and HOMA-IR were negatively correlated with birth weight. CONCLUSIONS: Low-birth-weight Pimas are thinner at ages 5-29 years, yet they are more insulin resistant relative to their body size than those of normal birth weight. By contrast, those with high birth weight are more obese but less insulin resistant relative to their body size. The insulin resistance of low-birth-weight Pima Indians may explain their increased risk for type 2 diabetes.

Adolescent↗
PubMed1999

Metabolic and immunologic effects of insulin lispro in gestational diabetes.

OBJECTIVE: To compare the immunologic response to insulin lispro with that to regular human insulin, thereby assuring its safety for use in women with gestational diabetes, and to verify that it is effective. RESEARCH DESIGN AND METHODS: We compared the metabolic and immunologic effects of insulin lispro and regular human insulin in 42 women >18 years of age diagnosed with gestational diabetes by oral glucose tolerance testing at 14-32 weeks of gestation. Patients were randomized to receive regular human insulin or insulin lispro before consuming a test meal. Serum insulin, blood glucose, and C-peptide concentrations were measured. Throughout the remainder of gestation, patients received premeal insulin lispro or regular human insulin combined with basal insulin and performed blood glucose self-monitoring before and after each meal. Insulin antibodies and HbA1c were determined at enrollment and 6 weeks later. In addition, 10 patients received continuous intravenous insulin (4 lispro, 6 regular human insulin) and dextrose infusions intrapartum to assess placental insulin transfer. RESULTS: Anti-insulin antibody levels were similar in the two groups. Insulin lispro was not detectable in the cord blood. During a meal test, areas under the curve for glucose, insulin, and C-peptide were significantly lower in the lispro group. Mean fasting and postprandial glucose concentrations and end point HbA1c were similar in the two groups. The lispro group demonstrated fewer hypoglycemic episodes (symptoms and blood glucose concentrations <55 mg/dl). No fetal or neonatal abnormalities were noted in either treatment group. CONCLUSIONS: Insulin lispro may be considered a treatment option for women with gestational diabetes.

Adult↗
PubMed1998

Randomized clinical trial of lifestyle interventions in Pima Indians: a pilot study.

A pilot trial was conducted to test adherence to specific lifestyle interventions among Pima Indians of Arizona, and to compare them for changes in risk factors for diabetes mellitus. Ninety-five obese, normoglycaemic men and women, aged 25-54 years, were randomized to treatments named 'Pima Action' (Action) and 'Pima Pride' (Pride), which were tested for 12 months. Action involved structured activity and nutrition interventions, and Pride included unstructured activities emphasizing Pima history and culture. Adherence to interventions, changes in self-reported activity and diet, and changes in weight, glucose concentrations, and other risk factors were assessed regularly. Thirty-five eligible subjects who had declined randomization were also followed as an 'observational' group and 22 members of this group were examined once at a median of 25 months for changes in weight and glucose concentration. After 12 months of intervention, members of both intervention groups reported increased levels of physical activity (median: Action 7.3 h month(-1), Pride 6.3 h month(-1), p < 0.001 for each), and Pride members reported decreased starch intake (28 g, p = 0.008). Body mass index, systolic and diastolic blood pressures, weight, 2-h glucose and 2-h insulin had all increased in Action members (p < 0.003 for each), and waist circumference had decreased in Pride members (p = 0.05). Action members gained more weight than Pride members (2.5 kg vs 0.8 kg, p = 0.06), and had a greater increase in 2-h glucose than Pride members (1.33 mM vs 0.03 mM, p = 0.007). Members of the observational group gained an average of 1.9 kg year(-1) in weight and had an increase of 0.36 mM year(-1) in 2-h glucose. Sustaining adherence in behavioural interventions over a long term was challenging. Pimas may find a less direct, less structured, and more participative intervention more acceptable than a direct and highly structured approach.

Adult↗
PubMed1998

Increasing prevalence of Type II diabetes in American Indian children.

Until recently, Type II diabetes was considered rare in children. The disease is, however, increasing among children in populations with high rates of Type II diabetes in adults. The prevalence of Type II diabetes was determined in 5274 Pima Indian children between 1967 and 1996 in three 10-year time periods, for age groups 5-9, 10-14 and 15-19 years. Diabetes was diagnosed using World Health Organisation criteria, based on an oral glucose tolerance test. The prevalence of diabetes increased over time in children aged 10 years and over: in boys from 0 % in 1967-1976 to 1.4% in 1987-1996 in the 10-14 year old age group, and from 2.43% to 3.78% for age group 15-19 and in girls from 0.72 % in 1967-1976 to 2.88 % in 1987-1996 in the 10-14 year old age group, and from 2.73 % to 5.31 % for age group 15-19 years. Along with the increase in the prevalence of Type II diabetes (p < 0.0001), there was an increase in weight (calculated as percentage of relative weight, p < 0.0001), and in frequency of exposure to diabetes in utero (p < 0.0001). The increasing weight and increasing frequency of exposure to diabetes in utero accounted for most of the increase in diabetes prevalence in Pima Indian children over the past 30 years. Type II diabetes is now a common disease in American Indian children aged 10 or more years and has increased dramatically over time, along with increasing weight. A vicious cycle related to an increase in the frequency of exposure to diabetes in utero appears to be an important feature of this epidemic.

Adolescent↗