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Jonathan Krakoff

Publications and source records attributed to Jonathan Krakoff.

18 recordsLinked to original sources

Acute insulin response is an independent predictor of type 2 diabetes mellitus in individuals with both normal fasting and 2-h plasma glucose concentrations.

BACKGROUND: Earlier prospective studies have identified insulin action and secretion as predictors of T2DM in populations with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) (2-h OGTT < 7.8 and 7.8-11 mmol/L, respectively). Fasting plasma glucose (FPG), an additional and recently modified (normal <5.6 mmol/L) diagnostic criterion is associated with insulin secretion. We wanted to establish whether insulin secretion persists as an independent predictor of T2DM in individuals with no clinical evidence of impaired glucose regulation based on FPG and 2-h plasma glucose concentrations. METHODS: Insulin action (M, euglycemic-hyperinsulinemic clamp), insulin secretion (acute insulin response (AIR), IVGTT), and adiposity (%Fat, DXA or densitometry) were compared at baseline in 358 Pima Indians (232M/126F, 18-44 years old) with normal glucose regulation of whom 61 (35M/26F) developed diabetes (DIAB) during a median follow-up time of 7.6 years. RESULTS: In proportional-hazard analysis, % Fat (HR = 1.52, p = 0.03), M (HR = 0.51, p = 0.04) and AIR (HR = 0.64, p = 0.003) predicted the development of diabetes after adjustment for age and sex. In regression analysis adjusting for age, sex, %Fat and M at baseline, the non-diabetic group (NON-DM) had a higher AIR (p = 0.0002) than the DIAB group; the positive association of AIR with adiposity observed in the NON-DM group was absent in the DIAB group. Cumulative incidence rates (12y) for diabetes were highest (48%) in subjects with both M and AIR below the population median and lowest (11%) in subjects with both M and AIR above the population median. CONCLUSION: AIR can predict diabetes prior to the current clinical indicators of impaired glucose regulation.

Adiposity↗

Relationships between plasma leptin concentrations and human brain structure: a voxel-based morphometric study.

We have previously demonstrated that obese people have reduced grey matter (GM) in several brain areas, including regions implicated in the regulation of taste (i.e., inferior frontal operculum and postcentral gyrus), reward (i.e., putamen), and behavioural processing (i.e., middle frontal gyrus), compared with their lean counterparts. It is well established that the brain may serve as a direct target for adiposity signals, one of the most important being leptin. We investigated the relationships between fasting plasma leptin concentrations and brain tissue composition in a group of 32 young adult Caucasians (12M/20F, age 32+/-1 years, body fat 29+/-1%, mean+/-S.E.) with normal glucose tolerance by using voxel-based morphometry of magnetic resonance imaging scans. Fasting plasma leptin concentrations were positively correlated with GM volumes of the left cerebellum and left inferior temporal gyrus and negatively associated with GM volumes of the left inferior frontal operculum, left postcentral gyrus, and right putamen (P<0.001, uncorrected for multiple comparisons) after adjustment for sex, percent body fat, age, fasting plasma insulin concentrations (i.e., the major determinants of plasma leptin), and global GM volume (thus allowing for an assessment of regional effects only). This study showed an independent, negative correlation between fasting plasma leptin concentrations, which are increased in obesity, and the volumes of GM in brain areas where obese people have reduced GM compared to their lean counterparts. These relationships may explain some of the abnormalities in brain morphology recently found to be associated with excess body fatness.

Adolescent↗

Effect of youth-onset type 2 diabetes mellitus on incidence of end-stage renal disease and mortality in young and middle-aged Pima Indians.

CONTEXT: The long-term outcome of persons with youth-onset type 2 diabetes mellitus has not been well described. OBJECTIVE: To compare incidence of diabetic end-stage renal disease (ESRD) and mortality in Pima Indians with youth- and older-onset type 2 diabetes mellitus. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal population-based study conducted between 1965 and 2002 in Pima Indians from the state of Arizona. Participants were divided into 2 groups: (1) youth-onset type 2 diabetes mellitus (onset <20 years of age) and (2) older-onset type 2 diabetes mellitus (onset > or =20 - <55 years of age). Events and person-years of follow-up were stratified in a time-dependent fashion by decades of age. End-stage renal disease was defined as dialysis attributed to diabetic nephropathy or death from diabetic nephropathy. MAIN OUTCOME MEASURES: Incidence rate of diabetic ESRD and mortality between 25 and 55 years of age, according to age at onset of type 2 diabetes mellitus. RESULTS: Among the 1856 diabetic participants, 96 had youth-onset type 2 diabetes mellitus. The age-sex-adjusted incidence of diabetic ESRD was 25.0 cases per 1000 person-years (95% confidence interval [CI], 6.7-43.1) in youth-onset diabetes mellitus and 5.4 cases per 1000 person-years (95% CI, 4.4-6.4) in older-onset diabetes mellitus (incidence rate ratio, 4.6; 95% CI, 2.2-9.8). Age-specific incidence rates were higher in participants with youth-onset diabetes mellitus at all ages. Between 25 and 55 years of age, the age-sex-adjusted death rate from natural causes was 15.4 deaths per 1000 person-years (95% CI, 0.2-30.5) in participants with youth-onset diabetes mellitus and 7.3 deaths per 1000 person-years (95% CI, 5.9-8.7) in individuals with older-onset diabetes mellitus (death rate ratio, 2.1; 95% CI, 0.8-5.7). Compared with nondiabetic participants, the death rate was 3.0 times as high in individuals with youth-onset diabetes mellitus (95% CI, 1.1-8.0) and 1.4 times as high in individuals with older-onset diabetes mellitus (95% CI, 1.1-1.8). In a subset of 1386 participants with complete data for all covariates who were observed from the onset of diabetes mellitus, the age at onset of diabetes mellitus was not associated with the incidence of ESRD (hazard ratio, 1.0; 95% CI, 0.9-1.2) after adjusting for sex, mean arterial pressure, body mass index (calculated as weight in kilograms divided by height in meters squared), plasma glucose concentration, smoking, hypoglycemic medicines, and blood pressure medicines in a Cox proportional-hazards model. CONCLUSIONS: Early-onset type 2 diabetes mellitus is associated with substantially increased incidence of ESRD and mortality in middle age. The longer duration of diabetes mellitus by middle age in individuals diagnosed younger than age 20 years largely accounts for these outcomes.

Adolescent↗

Lower total fasting plasma adiponectin concentrations are associated with higher metabolic rates.

CONTEXT: The possible role of adiponectin, a protein uniquely produced by the adipose tissue and significantly reduced in obesity and other insulin-resistant states, in the regulation of energy expenditure (EE) is still poorly understood. OBJECTIVE: The objective of the study was to investigate the relationship between total fasting plasma adiponectin concentrations and the various components of EE measured in a metabolic chamber in Pima Indians and to test whether body fat distribution may have a role in this association. DESIGN: This was a cross-sectional study. SETTING: The study was an inpatient clinical research unit. PARTICIPANTS: Sixty nondiabetic Pima Indians (45 males and 15 females), aged 18-45 yr, spanning a wide range of adiposity (body mass index 19.6-46.2 kg/m(2)) participated in the study. MAIN OUTCOME MEASURES: Total fasting plasma adiponectin concentrations, EE (24-h respiratory chamber), insulin sensitivity (euglycemic-hyperisulinemic clamp), body composition (dual-energy x-ray absorptiometry), and body fat distribution (waist to thigh ratio) were the main outcome measures. RESULTS: Total fasting plasma adiponectin concentrations are negatively associated with sleep EE adjusted for sex, age, fat-free mass, and fat mass. This correlation is still significant, although attenuated, after inclusion of insulin-stimulated glucose disposal among the regressors and further attenuated when adjusted also for waist to thigh ratio. CONCLUSIONS: The decrease in total fasting plasma adiponectin concentrations that accompanies fat accumulation may be a mechanism to prevent further weight gain by decreasing insulin sensitivity and increasing energy expenditure.

Adiponectin↗

Higher fasting plasma concentrations of glucagon-like peptide 1 are associated with higher resting energy expenditure and fat oxidation rates in humans.

BACKGROUND: Glucagon-like peptide 1 (GLP-1) is a gut hormone that decreases appetite and promotes satiety. Its role in energy metabolism regulation is still poorly understood. OBJECTIVE: The aim of the study was to investigate the relation of fasting plasma GLP-1 concentrations to rates of energy expenditure (EE) and substrate oxidation-ie, respiratory quotient (RQ). DESIGN: Forty-six glucose-tolerant white subjects (22 men, 24 women) aged 18-49 y whose adiposity spanned a wide range [body mass index (in kg/m2): 18.5-50] were studied in an inpatient clinic. Main outcome measures included resting EE and RQ (ventilated hood technique), body composition (dual-energy X-ray absorptiometry), and fasting plasma concentrations of GLP-1, pancreatic polypeptide, glucose, and insulin. RESULTS: Fasting plasma GLP-1 concentrations were positively associated with resting EE (after adjustment for age, sex, and body composition) and negatively correlated with RQ (after adjustment for age, sex, and percentage body fat) and fasting plasma pancreatic polypeptide concentrations (both before and after adjustment for age, sex, percentage body fat, and fasting plasma glucose and insulin concentrations). Adjustment for fasting plasma pancreatic polypeptide concentrations, a marker of parasympathetic outflow to the gut, attenuated the strength of the association of fasting plasma GLP-1 concentrations with resting EE and RQ. CONCLUSIONS: Higher fasting plasma GLP-1 concentrations are associated with higher rates of EE and fat oxidation independent of age, sex, and body composition. The autonomic nervous system may have a role in this relation. This effect, along with the established role of GLP-1 in promoting satiety, may further foster its therapeutic potential in the treatment of obesity.

Absorptiometry, Photon↗

Less activation of the left dorsolateral prefrontal cortex in response to a meal: a feature of obesity.

BACKGROUND: In an exploratory positron emission tomography study of postprandial regional cerebral blood flow, which is a marker of neuronal activity, obese men differed from lean men in several brain regions, including the prefrontal cortex. The subjects received a meal proportional to their body size; therefore, the meal volume was different for each person. OBJECTIVE: We investigated whether differences in the brain responses of obese and lean men to a meal represent satiety or feelings of gastric distension. DESIGN: We studied 9 lean (x +/- SD body fat: 15 +/- 5%; age: 33 +/- 10 y) and 9 obese (body fat: 31 +/- 4%; age: 32 +/- 10 y) men given a fixed amount (400 mL) of a liquid meal. We compared their results with those in 11 lean (body fat: 16 +/- 5%; age: 35 +/- 8 y) and 11 obese (body fat: 33 +/- 5%; age: 28 +/- 5 y) previously studied men given a meal proportional to their body size. We performed analyses by using a two-level, random-effects approach in the STATISTICAL PARAMETRIC MAPPING software package and a significance level of P < or = 0.001, uncorrected for multiple comparisons. RESULTS: Compared with lean men, obese men had consistently less postprandial activation in the left dorsolateral prefrontal cortex, irrespective of meal size. CONCLUSION: Because the dorsolateral prefrontal cortex has been implicated in the inhibition of inappropriate behavior, satiety, and meal termination, differential responses of neuronal activity to food intake in this area may contribute to a propensity for obesity or to the difficulty in losing weight experienced by obese men.

Adult↗

Effects of binge eating on satiation, satiety, and energy intake of overweight children.

BACKGROUND: Children who report episodes of binge eating gain more weight than do children not reporting binge eating. However, how binge eating affects children's food intake at meals is unknown. OBJECTIVE: We compared the energy intake and postmeal satiety of children with and without a history of binge eating during buffet meals. DESIGN: Sixty overweight children aged 6-12 y were categorized into those reporting past binge-eating episodes (n = 10) and those reporting no such episodes (n = 50). Children selected lunch twice from a multiple-item, 9835 kcal, buffet meal: after an overnight fast and after a standardized breakfast. Children ate ad libitum, until they reported they were full. The main outcome measures were energy intake during meals and duration of postmeal satiety, after adjustment for covariates, including age, race, sex, socioeconomic status, and body composition. RESULTS: After the overnight fast, children in the binge-eating group consumed more energy [x (+/-SD): 1748 +/- 581 compared with 1309 +/- 595 kcal; P = 0.04] and exhibited a shorter satiety duration (194 +/- 84 compared with 262 +/- 89 min; P = 0.03) than did children in the non-binge-eating group. After the standardized breakfast, binge-eating children reported a shorter satiety duration (75 +/- 62 compared with 132 +/- 62 min; P = 0.01) and consumed more energy at the postbreakfast meal (1874 +/- 560 compared with 1275 +/- 566 kcal; P = 0.004). CONCLUSION: The ability to consume large quantities of palatable foods, coupled with decreased subsequent satiety, may play a role in the greater weight gain found in binge-eating children.

Bulimia↗

Predominant effect of kidney disease on mortality in Pima Indians with or without type 2 diabetes.

BACKGROUND: We examined the effect of kidney disease (KD) on mortality in nondiabetic and diabetic Pima Indians aged > or = 45 years old. METHODS: Deaths and person-years of follow-up were stratified in a time-dependent fashion into categories of (1) no proteinuria and normal serum creatinine (SCr); (2) proteinuria and normal SCr; (3) high SCr [SCr > or = 133 micromol/L (1.5 mg/dL) in men, > or = 124 micromol/L (1.4 mg/dL) in women] but not on renal replacement therapy (RRT); or (4) RRT. RESULTS: Among 1993 subjects, 55.8% had type 2 diabetes at baseline. Overall death rates increased with declining kidney function in both the nondiabetic and diabetic subjects (P < 0.0001). Death rates were similar in nondiabetic and diabetic subjects with comparable levels of kidney function, although the number of deaths among nondiabetic subjects with advanced KD was small. Infections and malignancy were the leading causes of death in nondiabetic subjects with KD. Among diabetic subjects, overall mortality increased with diabetes duration (P = 0.0001) and was highest in those on RRT (P < 0.0001). High SCr was associated with higher death rates from cardiovascular disease (CVD), diabetic nephropathy (DN), infections, and malignancy. CONCLUSION: Death rates increased comparably with worsening kidney function in both nondiabetic and diabetic subjects and were similar in nondiabetic and diabetic subjects without KD. KD was associated with excess mortality from DN, CVD, infections, and malignancy in diabetic subjects, and from infections in those without diabetes.

Adult↗

Early growth in offspring of diabetic mothers.

OBJECTIVE: By age 5 years, offspring of diabetic mothers (ODMs) are heavier and have altered glucose metabolism compared with offspring of mothers without diabetes (non-DMs). This study evaluates the growth pattern of ODMs before the age of 5 years. RESEARCH DESIGN AND METHODS: Anthropometric measures (z scores) from birth, 1.5 years, and 7.7 years in Pima Indian children were compared by maternal diabetes status. RESULTS: After adjustment for earlier gestational age at delivery (37.8 vs. 39.3 weeks, P < 0.01), ODMs were heavier at birth (z score birth weight 0.49 vs. -0.04, P < 0.01) than non-DMs. At age 1.5 years, ODMs were shorter than the non-DMs (z score = -0.24 vs. 0.12, P < 0.01) but their weight and relative weight (RW; weight adjusted for age, sex, and length or height) were similar. From birth to 1.5 years, ODMs showed significant "catch down" of weight compared with non-DMs (change in weight z score from birth to 1.5 years of ODMs and non-DMs was -0.56 and 0.12, respectively, P < 0.01). By age 7.7 years, ODMs were heavier (weight z score 0.89 vs. -0.07, P < 0.01) but had similar height as non-DMs. Differences in glucose and insulin concentrations at age 7.7 years were dependent on RW. CONCLUSIONS: ODMs had a dramatically different growth pattern from that of non-DMs. Gestational age-adjusted birth weight was higher. During the first 1.5 postnatal years, the change in weight z score and attained height were reduced. Subsequently, height caught up to that of non-DMs, while weight gain greatly exceeded that of non-DMs.

Birth Weight↗

Adiponectin concentrations are influenced by renal function and diabetes duration in Pima Indians with type 2 diabetes.

Adiponectin is produced exclusively by adipocytes, and its serum concentration is inversely associated with adiposity. This study examines the relationship among diabetes, renal function, and serum adiponectin in Pima Indians. Serum adiponectin was measured in 1069 people in whom glycemia and renal function had been measured. Serum adiponectin, adjusted for age, sex, and body mass index, was lowest in those with impaired glucose regulation or diabetes of less than 10 yr duration and highest in those with normal glucose tolerance or diabetes of duration of at least 10 yr. Both urinary albumin to creatinine ratio (ACR) and serum creatinine were positively correlated with adiponectin (Spearman's r = 0.43; P < 0.0001, and r = 0.37; P < 0.0001, respectively) in diabetic subjects. After stratification by albuminuria (normoalbuminuria ACR < 30 mg/g, microalbuminuria ACR = 30-299 mg/g, and macroalbuminuria ACR >or= 300 mg/g), the highest adiponectin concentration was in the macroalbuminuria group (geometric mean = 9.6 microg/ml) and the lowest was in the normoalbuminuric group (geometric mean = 5.6 microg/ml). After adjustment for age, sex, body mass index, and diabetes duration, the serum adiponectin concentration in the macroalbuminuria group was significantly higher than in both other groups (P < 0.0001). Serum adiponectin is lowest in the presence of impaired glucose regulation and early diabetes. In the presence of diabetes, serum adiponectin is positively associated with abnormal renal function and diabetes duration.

Adiponectin↗

Genome-wide linkage analysis of serum adiponectin in the Pima Indian population.

Adiponectin is a circulating protein secreted by adipocytes and is thought to have insulin-sensitizing effects. We present genetic analysis of adiponectin levels in 517 Pima Indians without diabetes (from 162 families, 750 sib-pairs). Adiponectin concentrations were heritable, with 39% of the variance of age- and sex-adjusted adiponectin potentially accounted for by additive genetic influences in this population. In genome-wide linkage analyses, suggestive linkage (logarithm of odds [LOD] = 3.0) of adiponectin adjusted for age and sex was found on chromosome 9p at 18 cM. Linkage was also present after inclusion of adiponectin concentrations of siblings with type 2 diabetes not treated pharmacologically (total siblings 582, 182 families, 860 sib-pairs: LOD = 3.5). Tentative evidence of linkage was also found on chromosomes 2 (LOD = 1.7 at 89 cM), 3 (LOD = 1.9 at 124 cM), and 10 (LOD = 1.7 at 70 cM), offering some support to findings of a previous genome-wide scan of adiponectin. Our data suggest that quantitative trait loci on chromosomes 2, 3, 9, and 10 may influence circulating adiponectin concentrations in the Pima population.

Adiponectin↗

Incidence of retinopathy and nephropathy in youth-onset compared with adult-onset type 2 diabetes.

OBJECTIVE: To examine the risk of retinopathy and nephropathy in participants in whom type 2 diabetes was diagnosed in youth (before 20 years of age) compared with those in whom type 2 diabetes was diagnosed at older ages. RESEARCH DESIGN AND METHODS: Subjects in whom youth-onset or adult-onset diabetes was diagnosed in the longitudinal study of health in the Pima Indians of Arizona were followed for microvascular complications. Diabetes was diagnosed in 178 subjects before 20 years of age (youth), in 1,359 subjects at 20-39 years of age (younger adults), and in 971 subjects at 40-59 years of age (older adults). Incidence rates of diabetic retinopathy diagnosed by direct ophthalmoscopy through dilated pupils and nephropathy (protein-to-creatinine ratio > or =0.5 g/g) were calculated by age at diagnosis. RESULTS: Over 25 years, nephropathy developed in 35 of the participants with youth-onset type 2 diabetes; this incidence rate was not significantly different from that in patients with adult-onset diabetes (P = 0.77). Incidence rates of retinopathy, however, were significantly lower for the youth-onset group (P = 0.007). Adjusted for sex, glycemia, and blood pressure, risk of retinopathy was lower in patients with youth-onset diabetes than in those with adult-onset diabetes (hazard rate ratio [HRR] 0.42, 95% CI 0.24-0.74, P = 0.003), but risk of nephropathy was not different (HRR 1.2, 95% CI 0.77-1.3, P = 0.38). CONCLUSIONS: In Pima Indians, the risk of nephropathy as a function of duration of diabetes is similar in all age groups. By contrast, the risk of retinopathy is lower in patients with youth-onset type 2 diabetes.

Adult↗

Longitudinal studies of incidence and progression of diabetic retinopathy assessed by retinal photography in pima indians.

OBJECTIVE: To examine incidence and progression of retinopathy using retinal photographs in Pima Indians and to compare the results with those obtained when retinopathy is assessed by direct ophthalmoscopy. RESEARCH DESIGN AND METHODS: We undertook an analysis of examinations conducted between 1 April 1982 and 31 December 1990 in residents of the Gila River Community in central Arizona. Data were taken from 411 people with diabetes who had at least two examinations during this period. Incidence and progression of retinopathy were evaluated by retinal photography and fundoscopy, and hazard rate ratios were calculated for various potential risk factors measured at baseline. RESULTS: Previously diagnosed retinopathy tended to progress, except in individuals with minimal nonproliferative retinopathy, among whom follow-up examinations were more likely to show no retinopathy. Diabetes duration (hazard rate ratio [HRR], 1.06 per year difference [P = 0.007]), hyperglycemia (HbA(1) HRR, 1.27 per 1% difference [P < 0.0001]), the type of treatment for diabetes (insulin use HRR, 3.06 [P = 0.0007], and oral hypoglycemic use HRR, 2.40 [P = 0.0034], compared with individuals on no pharmacotherapy), and macroalbuminuria (HRR, 2.86, compared with individuals without macroalbuminuria [P = 0.0486]) were associated with the development of retinopathy. Although fundoscopy detected fewer cases of retinopathy, HRRs for most risk factors were similar when retinopathy was assessed by fundoscopy rather than retinal photography. CONCLUSIONS: Although retinopathy tends to worsen over time, some eyes show improvement, especially in patients with minimal nonproliferative retinopathy. As in other populations, glycemic control is the major modifiable risk factor for the development and progression of retinopathy.

Adolescent↗

Inflammatory markers, adiponectin, and risk of type 2 diabetes in the Pima Indian.

OBJECTIVE: To examine the association between adiponectin, a known predictor of diabetes in Pima Indians, and markers of inflammation and endothelial function in nondiabetic subjects and to assess whether these markers predict later diabetes in a case-control study within a longitudinal health study in Pima Indians. RESEARCH DESIGN AND METHODS: Participants with normal glucose tolerance at baseline were selected. Case subjects (who later developed type 2 diabetes), and control subjects (n = 71 pairs) were matched for BMI, age, and sex. Adiponectin, C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor-alpha, phospholipase A2 (sPLA2), soluble E-selectin (SE-selectin), soluble intracellular adhesion molecule-1, soluble vascular adhesion molecule-1, and von Willebrand factor (vWF) were measured in baseline samples. RESULTS: Adiponectin was negatively correlated with CRP (r = -0.25, P < 0.05), IL-6 (r = -0.20, P < 0.05), sPLA2 (r = -0.22, P < 0.05), and SE-selectin (r = -0.20, P < 0.05). CRP and IL-6 did not predict diabetes. Only vWF predicted the development of diabetes (incidence rate ratio 0.67 for a 1-SD difference, 95% CI 0.41-1.00, P = 0.05), but this was not significant after adjustment for age, glucose, HbA(1c), waist circumference, and fasting insulin (hazard rate ratio 0.73, 95% CI 0.46-1.16, P = 0.18). CONCLUSIONS: Adiponectin is negatively correlated with markers of inflammation in vivo. In case and control subjects matched for BMI, with the exception of vWF, none of the inflammatory markers predicted diabetes. Adiponectin may be the link between adiposity, inflammation, and type 2 diabetes.

Adiponectin↗

Adiponectin and development of type 2 diabetes in the Pima Indian population.

Adiponectin is a collagen-like circulating protein secreted by adipocytes that is proposed to mediate obesity-related resistance to insulin. In a case-control series, we assessed the role of adiponectin in later development of type 2 diabetes in 70 patients who later developed type 2 diabetes and 70 controls, matched for body-mass index, age, and sex. Cases and controls were taken from the longitudinal study of health in the Pima Indian population. At baseline, the concentration of adiponectin was lower in cases than in controls (p=0.01) and individuals with high concentrations of this protein were less likely to develop type 2 diabetes than those with low concentrations (incidence rate ratio 0.63 [95% CI 0.43-0.92]; p=0.02).

Adiponectin↗

Low plasma adiponectin concentrations do not predict weight gain in humans.

Low concentrations of plasma adiponectin, the most abundant adipose-specific protein, are observed in obese individuals and predict the development of type 2 diabetes. Administration of adiponectin to rodents prevented diet-induced weight gain, suggesting a potential etiologic role of hypoadiponectinemia in the development of obesity. Our aim was to prospectively examine whether low plasma adiponectin concentrations predict future weight gain in Pima Indians, explaining the predictive effect of adiponectin on the development of type 2 diabetes. We measured plasma adiponectin concentrations in 219 nondiabetic Pima Indians (112 M/107 F, age 31 +/- 9 years, body weight 96 +/- 20 kg [mean +/- SD]) in whom body weight and height were measured and BMI calculated at baseline and follow-up. Cross-sectionally, plasma adiponectin concentrations were negatively associated with body weight (r = -0.28, P = 0.0001). Prospectively, plasma adiponectin concentrations at baseline were not associated with change in weight or BMI before or after adjustment for time of follow-up or after additional adjustment for age at follow-up and sex (all P > 0.3). Our data suggest that low plasma adiponectin concentrations do not play an etiologic role in development of obesity in Pima Indians. Therefore, the predictive effect of low plasma adiponectin concentrations on the development of type 2 diabetes seems to be mediated by factors other than increased adiposity.

Adiponectin↗