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R L Hanson

Publications and source records attributed to R L Hanson.

At least 37 records · Page 2Linked to original sources

Gamma globulin levels predict type 2 diabetes in the Pima Indian population.

It has been proposed that inflammation or infection may contribute to the development of type 2 diabetes. We examined whether serum gamma globulin, a nonspecific measure of the humoral immune system, predicted changes in glucose tolerance in 2,530 members of the Pima Indian population, a group with a marked predisposition to type 2 diabetes. Cross-sectionally, gamma globulin was positively related to age (r = 0.08, P < 0.0005), BMI (r = 0.09; P < 0.0001), and female sex (P < 0.0001). Gamma globulin concentrations were familial, being positively correlated among siblings (r = 0.23; P < 0.0001) and between parents and their children (mother/child: r = 0.17, P < 0.0001; father/child: r = 0.25, P < 0.0001). Gamma globulin concentrations were higher with greater degrees of American Indian heritage (P < 0.004, with adjustment for age, sex, and BMI) and in the presence of a family history of type 2 diabetes (P < 0.04). Higher gamma globulin levels predicted risk of diabetes. In univariate analysis, a 1 SD difference in gamma globulin was associated with a 20% higher incidence of diabetes in those who were normal glucose tolerant at baseline (hazard rate ratio 1.20 [CI 1.11-1.30]; P < 0.0001) and remained as a significant predictor of diabetes, even when controlled for effects of sex, BMI, and 2-h glucose as additional predictors (hazard rate ratio for 1 SD difference in gamma globulin, 1.14 [1.05-1.24]; P = 0.002). Gamma globulin was also associated in univariate analysis with later development of impaired glucose tolerance (IGT) (hazard rate ratio 1.15 [1.07-1.23]; P < 0.0001), but not with the transition from IGT to diabetes (hazard rate ratio 1.04 [0.90-1.20]; P = 0.6). Thus, gamma globulin levels predict increased risk of diabetes in the Pima population. We suggest that immune function or activation may play a role in the development of type 2 diabetes.

Adult↗

Changes in BMI and weight before and after the development of type 2 diabetes.

OBJECTIVE: To examine weight changes occurring before and after the diagnosis of diabetes and the association of these changes with treatment and microvascular complications. RESEARCH DESIGN AND METHODS: We undertook an analysis of serial examinations conducted between 1965 and 2000 in residents of the Gila River Community in Central Arizona. Data were taken from 4,226 examinations of 816 individuals in whom diabetes developed over the course of a longitudinal study and who had undergone a nondiabetic examination within 4 years preceding diagnosis. We measured changes in BMI between examinations. RESULTS: Before diagnosis of diabetes, there were steady gains in weight: mean BMI climbed between 0.43 and 0.71 kg/m(2) per year. After diagnosis, the weight gain declined, and weight loss was generally seen; the mean rate of change of BMI ranged between -0.61 and +0.22 kg/m(2) per year. When current treatment was considered, there was greater weight stability in individuals taking insulin compared with those not taking hypoglycemic medication. Medication was a statistically significant factor for change in weight for most of the time intervals analyzed. There was no statistically significant association with retinopathy or nephropathy. CONCLUSIONS: Before development of diabetes, there was a progressive rise in weight, and after diagnosis, there was a tendency toward weight loss. Weight-loss interventions in individuals with diabetes will need to account for this tendency if they are to successfully modify the course of the disease.

Administration, Oral↗

The effect of Indian or Anglo dietary preference on the incidence of diabetes in Pima Indians.

OBJECTIVE: In short-term studies, adoption of a traditional diet is associated with reduction in metabolic abnormalities often found in populations experiencing rapid lifestyle changes. We examined the long-term effects of a self-assessed traditional or nontraditional dietary pattern on the development of type 2 diabetes in 165 nondiabetic Pima Indians. RESEARCH DESIGN AND METHODS: Dietary intake was assessed in 1988 by a quantitative food frequency method, and subjects were asked to classify their diet as "Indian," "Anglo," or "mixed." The Indian diet reflects a preference for Sonoran-style and traditional desert foods. The Anglo diet reflects a preference for non-Sonoran-style foods typical of the remaining regions of the U.S. RESULTS: In women, the intake of complex carbohydrates, dietary fiber, insoluble fiber, vegetable proteins, and the proportion of total calories from complex carbohydrate and vegetable proteins were significantly higher (P < 0.05) in the Indian than in the Anglo diet. The mixed diet was intermediate in of all these constituents. In men, the intake for these nutrients was also higher in the Indian than in the Anglo group, but not significantly. Diabetes developed in 36 subjects (8 men and 28 women) during 6.2 years of follow-up (range 0.9-10.9). The crude incidence rates of diabetes were 23. 35, and 63 cases per 1,000 person-years in the Indian. mixed, and Anglo groups, respectively. After adjustment for age, sex, BMI, and total energy intake in a proportional hazards model, the risk of developing diabetes in the Anglo-diet group was 2.5 times as high (95%) CI 0.9-7.2) and the rate in the mixed-diet group was 1.3 times as high (0.6-3.3) as in the Indian-diet group. CONCLUSIONS: This study suggests that the adoption of an Anglo diet may increase the risk of developing diabetes in Pima Indians, but it does not provide unequivocal evidence for or against this hypothesis.

Adolescent↗

Comparison of the effect of plasma glucose concentrations on microvascular disease between Pima Indian youths and adults.

OBJECTIVE: To examine whether the current adult guidelines for diagnosis of diabetes are applicable to youth (age <20 years). RESEARCH DESIGN AND METHODS: We analyzed fasting plasma glucose (FPG) and 2-h plasma glucose (PG) in two groups of Pima Indians, youths aged 5-19 years and adults aged 20-34 years, in relation to the incidence of microvascular disease when subjects were reexamined at ages 25-39 (youths) and 40-54 (adults). Microvascular disease was defined as retinopathy or a urine protein-to-creatinine ratio > or =0.5 g. RESULTS: An increase in the incidence of microvascular disease occurred at nearly the same level of glycemia in both groups. For youths, this increase occurred at FPG approximately 7.3 mmol/l and 2-h PG approximately 10.0 mmol/l; for adults, this increase occurred at FPG approximately 7.5 mmol/l and 2-h PG approximately 10.3 mmol/l. Sensitivity of the adult diagnostic guidelines of FPG > or =7.0 mmol/l and 2-h PG > or =11.1 mmol/l for the detection of microvascular disease was much lower (with higher specificity) in youths than in adults. Receiver operating characteristics (ROC) curve areas were lower for FPG and 2-h PG for youths, suggesting that microvascular disease was less strongly predicted by baseline glucose. CONCLUSION: The current adult guidelines for diagnosis of diabetes are applicable to youth, as they identify a population at high risk of microvascular complications.

Adolescent↗

Association of physical activity and serum insulin concentrations in two populations at high risk for type 2 diabetes but differing by BMI.

OBJECTIVE: Physical activity and insulin sensitivity are related in epidemiological studies, but the consistency of this finding among populations that greatly differ in body size is uncertain. The present multiethnic epidemiological study examined whether physical activity was related to insulin concentrations in two populations at high risk for diabetes that greatly differ by location, ethnic group, and BMI. RESEARCH DESIGN AND METHODS: The study populations consisted of 2,321 nondiabetic Pima Indian men and women aged 15-59 years from Arizona and 2,716 nondiabetic men and women aged 35-54 years from Mauritius. Insulin sensitivity was estimated by mean insulin concentration (average of the fasting and postload insulin), and total (i.e., leisure and occupational) physical activity was assessed by questionnaire. RESULTS: Pima men and women who were more active had significantly (P < 0.05) lower mean insulin concentrations than those less active (BMI and age-adjusted means were 179 vs. 200 and 237 vs. 268 pmol/l). Similar findings were noted in Mauritian men and women (94 vs. 122 and 127 vs. 148 pmol/l). In both populations, activity remained significantly associated with mean insulin concentration controlled for age, BMI, waist-to-thigh or waist-to-hip ratio, and mean glucose concentrations. CONCLUSIONS: Physical activity was negatively associated with insulin concentrations both in the Pima Indians, who tend to be overweight, and in Mauritians, who are leaner. These findings suggest a beneficial role of activity on insulin sensitivity that is separate from any influence of activity on body composition.

Adolescent↗

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↗

Regioselective enzymatic aminoacylation of lobucavir to give an intermediate for lobucavir prodrug.

Synthesis of lobucavir prodrug, L-valine, [(1S,2R,3R)-3-(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)-2-(hydroxymethyl) cyclobutyl]methyl ester monohydrochloride (BMS 233866), requires regioselective coupling of one of the two hydroxyl groups of lobucavir (BMS 180194) with valine. Either hydroxyl group of lobucavir could be selectively aminoacylated with valine by using enzymatic reactions. N-[(Phenylmethoxy)carbonyl]-L-valine, [(1R,2R,4S)-2-(2-amino-6-oxo-1H-purin-9-yl)-4-(hydroxymethyl)cyclobutyl]methyl ester (3, 82.5% yield), was obtained by selective hydrolysis of N,N'-bis[(phenylmethoxy)carbonyl]bis[L-valine], O,O'-[(1S,2R,3R)-3-(2-amino-6-oxo-1H-purin-9-yl)cyclobuta-1,2-diyl]methyl ester (1) with lipase M, and L-valine, [(1R,2R,4S)-2-(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)-4-(hydroxymethyl)cyclobutyl]methyl ester monohydrochloride (4, 87% yield) was obtained by hydrolysis of bis[L-valine], O,O'-[(1S,2R,3R)-3-(2-amino-6-oxo-1H-purin-9-yl)cyclobuta-1,2-diyl]methyl ester, dihydrochloride (2), with lipase from Candida cylindracea. The final intermediate for lobucavir prodrug, N-[(phenylmethoxy)carbonyl]-L-valine, [(1S,2R,4R)-3-(2-amino-6-oxo-1H-purin-9-yl)-2-(hydroxymethyl)cyclobutyl]methyl ester (5), could be obtained by transesterification of lobucavir using ChiroCLEC BL (61% yield), or more selectively by using immobilized lipase from Pseudomonas cepacia (84% yield).

Acylation↗

An autosomal genomic scan for loci linked to plasma leptin concentration in Pima Indians.

OBJECTIVE: To identify chromosomal regions linked to plasma leptin concentrations. DESIGN: Autosomal genome-wide scan, including 516 microsatellite markers. Sib-pair (Haseman-Elston) and variance components methods were used to assess genetic linkage. SUBJECTS: 770 Pima Indians comprising 239 nuclear families (for a total of 1199 sibling-pairs). MEASUREMENTS: Plasma leptin concentrations and body mass index (BMI), adjusted for age and sex. RESULTS: The strongest evidence for linkage with plasma leptin concentration was on chromosome 6p logarithm of odds (LOD) = 2.1 by variance components analysis). There was no evidence for linkage to BMI in this region. Additional regions with marginal evidence for linkage to plasma leptin concentration (LOD > or =1.0) were detected on chromosomes 3, 11, 13, 15 and 16. CONCLUSIONS: The results suggest that a locus on chromosome 6p influences plasma leptin concentrations. Replication studies are needed to exclude the possibility that linkage has been falsely detected.

Adolescent↗

Individual estimates of European genetic admixture associated with lower body-mass index, plasma glucose, and prevalence of type 2 diabetes in Pima Indians.

Individual genetic admixture estimates (IA) from European Americans (EAs) were computed in 7,996 members of the Gila River Indian Community (Arizona). Parental populations for the analysis were European Americans and full-heritage Pima Indians. A logistic regression was performed on 7,796 persons, to assess association of IA with type 2 diabetes. The odds ratio, comparing diabetes risk in full-heritage EAs with full-heritage Pima Indians, was 0.329 (95% confidence interval [CI] 0.225-0.482). Proportional-hazards analysis was performed on 5,482 persons who were nondiabetic at their first examination and 1,215 subjects who developed diabetes during the study. The hazard risk ratio for IA was 0.455 (95% CI 0.301-0.688). Nondiabetic persons had significantly more European IA. In nondiabetic Pimans, multivariate linear regressions of quantitative predictors of type 2 diabetes mellitus, including fasting plasma glucose, 2-h post-load plasma glucose, and body-mass index, showed significant inverse relations with IA when controlled for sex and age. These results illustrate the ongoing evolution of populations by the mechanism of gene flow and its effect on disease risk in the groups with admixture. When the two parental populations differ in disease prevalence, higher or lower risk is associated with admixture, depending on the origin of the admixed alleles and the relative magnitude of the disease prevalence in the parental populations. These data also illustrate the strong genetic components in type 2 diabetes and are consistent with one susceptibility locus common to obesity and diabetes.

Age Factors↗

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↗

A calpain-10 gene polymorphism is associated with reduced muscle mRNA levels and insulin resistance.

Previous linkage studies in Mexican-Americans localized a major susceptibility locus for type 2 diabetes, NIDDM1, to chromosome 2q. This evidence for linkage to type 2 diabetes was recently found to be associated with a common G-->A polymorphism (UCSNP-43) within the CAPN10 gene. The at-risk genotype was homozygous for the UCSNP-43 G allele. In the present study among Pima Indians, the UCSNP-43 G/G genotype was not associated with an increased prevalence of type 2 diabetes. However, Pima Indians with normal glucose tolerance, who have a G/G genotype at UCSNP-43, were found to have decreased rates of postabsorptive and insulin-stimulated glucose turnover that appear to result from decreased rates of glucose oxidation. In addition, G/G homozygotes were found to have reduced CAPN10 mRNA expression in their skeletal muscle. A decreased rate of insulin-mediated glucose turnover, or insulin resistance, is one mechanism by which the polymorphism in CAPN10 may increase susceptibility to type 2 diabetes mellitus in older persons.

Adolescent↗

A high fasting plasma insulin concentration predicts type 2 diabetes independent of insulin resistance: evidence for a pathogenic role of relative hyperinsulinemia.

Fasting hyperinsulinemia is a widely used surrogate measure of insulin resistance and predicts type 2 diabetes in various populations. Whether fasting hyperinsulinemia predicts diabetes independent of insulin resistance is unknown. In 319 Pima Indians with normal glucose tolerance, fasting plasma insulin concentration and insulin-stimulated glucose disposal (M) (hyperinsulinemic clamp) were inversely related, but at any given M, there was substantial variation, with some subjects being hyperinsulinemic and others being hypoinsulinemic relative to their degree of insulin sensitivity. In 262 of the 319 subjects followed prospectively over 6.4 +/- 3.9 years, a high fasting plasma insulin concentration was a significant independent predictor of diabetes, in addition to low M and low acute insulin response (AIR) (intravenous glucose challenge). In 161 of the 319 subjects with follow-up measurements of M and AIR (5.1 +/- 3.9 years), a high relative fasting plasma insulin concentration predicted a decline in AIR but not in M before the onset of diabetes. The adjusted fasting plasma insulin concentration was a familial trait (heritability of 0.52) and in a genome-wide scan, there was suggestive evidence of linkage (logarithm of odds score 1.77) to a region on chromosome 3q, which harbors the gene encoding GLUT2. These results provide the first prospective evidence in humans that fasting hyperinsulinemia itself has a primary role in the pathogenesis of diabetes, independent of insulin resistance. Whether amelioration of basal insulin hypersecretion will prevent diabetes remains to be elucidated.

Adult↗

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↗

Type 2 diabetes and low birth weight: the role of paternal inheritance in the association of low birth weight and diabetes.

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.

Adult↗

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↗

Mutations in the genes for hepatocyte nuclear factor (HNF)-1alpha, -4alpha, -1beta, and -3beta; the dimerization cofactor of HNF-1; and insulin promoter factor 1 are not common causes of early-onset type 2 diabetes in Pima Indians.

OBJECTIVE: Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous subtype of type 2 diabetes characterized by an early age at onset and autosomal dominant inheritance. MODY can result from heterozygous mutations in at least five genes. The purpose of this study was to determine whether alterations in known MODY genes and two MODY candidate genes contribute to the development of early-onset type 2 diabetes in Pima Indians. RESEARCH DESIGN AND METHODS: The coding regions of the known MODY genes hepatocyte nuclear factor (HNF)-1alpha, HNF-4alpha, HNF-1beta, and insulin promoter factor 1 and the coding regions of two MODY candidate genes, HNF-3beta and the dimerization cofactor of HNF-1, were sequenced in genomic DNA from Pima Indians. The primary "affected" study population consisted of 46 Pima Indians whose age at onset of type 2 diabetes was < or =20 years. DNA sequence variants identified in the affected group were then analyzed in a group of 80 "unaffected" Pima Indians who were at least 40 years old and had normal glucose tolerance. RESULTS: A total of 11 polymorphisms were detected in these genes. However, none of the polymorphisms differed in frequency among Pima Indians with an early age at onset of diabetes compared with older Pima Indians with normal glucose tolerance. CONCLUSIONS: Mutations in these known MODY or MODY candidate genes are not a common cause of early-onset diabetes in Pima Indians.

Adolescent↗

The 1997 American Diabetes Association and 1999 World Health Organization criteria for hyperglycemia in the diagnosis and prediction of diabetes.

OBJECTIVE: The 1997 American Diabetes Association (ADA) and the 1985 and 1999 World Health Organization (WHO) criteria for diabetes and hyperglycemia differ. The appropriateness of these diagnostic criteria in terms of individuals identified as abnormal and their prognosis has been debated. The purpose of this study is to compare the classifications of people by these criteria and to compare fasting and postload plasma glucose concentrations in the prediction of diabetes. RESEARCH DESIGN AND METHODS: The frequencies of diabetes by the 3 sets of criteria were compared in 5,023 adult Pima Indians not taking hypoglycemic drugs. Among nondiabetic subjects, fasting plasma glucose (FPG) and 2-h postload plasma glucose (2-h PG) concentrations and categories of impaired glucose regulation or diabetes were evaluated as predictors of diabetes defined by 1999 WHO criteria. RESULTS: The frequency of diabetes was 12.5% by 1997 ADA criteria, 14.6% by 1985 WHO criteria, and 15.3% by 1999 WHO criteria. The incidence of diabetes was strongly related to higher FPG and 2-h PG, each of which had very similar predictive powers. Impaired glucose tolerance (IGT) was more common than impaired fasting glucose (IFG) (15 vs. 5%), but the 5-year incidence of diabetes was higher in IFG than IGT (37 vs. 24%). CONCLUSIONS: The prevalence and incidence of diabetes are somewhat lower with the ADA criteria than with the 1985 or 1999 WHO criteria. The intermediate categories of glycemia differ substantially IFG defines a smaller number of people who are at higher risk of developing diabetes than those with IGT. More people at high risk of diabetes could be identified by using either IFG or IGT, as recommended by the 1999 WHO criteria, or by using the FPG concentration alone, but with a lower cutoff value.

Adult↗

Plasma glucose and prediction of microvascular disease and mortality: evaluation of 1997 American Diabetes Association and 1999 World Health Organization criteria for diagnosis of diabetes.

OBJECTIVE: The 1997 American Diabetes Association (ADA) and 1999 World Health Organization (WHO) criteria for diabetes and hyperglycemia were evaluated and compared with respect to prediction of microvascular and macrovascular disease and mortality RESEARCH DESIGN AND METHODS: The prevalence of retinopathy and nephropathy at baseline and during the subsequent 10 years and mortality rates were examined in relation to baseline fasting plasma glucose (FPG) and 2-h postload plasma glucose (2-h PG) among 5,023 Pima Indian adults and in relation to the cut points defined by the ADA and WHO criteria. RESULTS: The frequencies of retinopathy and nephropathy were directly related to baseline FPG and 2-h PG with approximate thresholds near or below the current diagnostic criteria for diabetes (FPG > or =7.0 and 2-h PG > or = 11.1 mmol/l). The rates of retinopathy were 4.7% in impaired fasting glucose (IFG) and 20.9% in diabetes by ADA criteria; 1.6% for impaired glucose tolerance (IGT) and 19.7% for diabetes by 1985 WHO criteria; and 1.2% for IGT and 19.2% for diabetes by the 1999 WHO criteria. Mortality rates from cardiovascular-renal-related diseases were higher in diabetic individuals (FPG > or =7.0 or 2-h PG > 11.1 mmol/l) than in those with normal FPG and 2-h PG but were not elevated in those with IFG or IGT. CONCLUSIONS: Retinopathy and nephropathy were directly related to higher FPG or 2-h PG. FPG, which identifies those at high risk of microvascular disease and mortality, can be used to predict these outcomes and to diagnose diabetes when oral glucose tolerance testing is not practical.

Adult↗