Prevalence of Bacillus cereus in dairy powders focusing on its toxigenic genes and antimicrobial resistance.

Bacillus cereus is a common environmental foodborne microorganism that is mainly found to harbor toxigenic genes with multiple antibiotic resistances and is linked to threatening the safety of dried milk in concern to powdered infant milk formula. In the current investigation, the mean value of B. cereus in 140 samples of powdered milk was 0.57 × 102 ± 0.182 × 102, 0.15 × 102 ± 0.027 × 102, 0.21 × 102 ± 0.035 × 102, and 0.32 × 102 ± 0.072 × 102 CFU/g in a percentage of 64.0 samples of whole milk powder, 43.3 of skim milk powder, 26.7 of powdered infant milk formula and 36.7 milk-cereal-based infant formula, respectively. The results revealed that B. cereus isolates were found to harbor toxigenic genes in the following percentages: 77.8, 2.0, 72.7, 16.2, and 67.7 for nhe, hbl, cytK, ces, and bceT, respectively. Despite all evaluated B. cereus strains were originated from dairy powders, they showed a significant difference (P < 0.05) in their harbored toxigenic cytK gene between whole and skim milk powders with powdered infant formula and milk-cereal-based infant formula, as well as between powdered infant formula and milk-cereal-based infant formula. All isolated B. cereus strains were resistant to cefoxitin, colistin sulfate, neomycin, trimethoprim-sulfamethoxazole, oxacillin, and penicillin. Based on the antimicrobial resistance of B. cereus strains to cephalothin, chloramphenicol, nalidixic acid, and tetracycline, there was a significant difference (P < 0.05) between powdered infant milk formula and whole milk powder strains. This survey is one of few studies proceeded in Egypt to determine the prevalence of toxigenic B. cereus strains in milk-cereal-based infant formula and powdered infant formula as well as skim milk powder.

Assessment of safety and quality aspects of boiling treatment of quail eggs.

A total of 300 quail eggs were collected randomly from different markets in Cairo and Giza Governorates. Five eggs were represented as one egg sample. Shell and content of each egg were examined for their microbiological contents, sensory evaluation and study of Escherichia coli O157 survival in artificially contaminated eggs. Moreover, qualitative detection of antimicrobial residues by seven plates microbiologically bioassay and confirmed by validated high-performance liquid chromatography (HPLC) methods for positively reacted antimicrobials in raw and boiled samples. There was a significant difference (P < 0·05) between the grading score of eggs after the boiling at 2-, 4-, 5- and 7-min. Based on the survival results, the refrigeration storage and boiling for 5 min of quail eggs was confirmed that such eggs are without E. coli O157. After the boil, the concentrations of oxytetracycline (OTC) and 4-Epi-OTC residues were significantly reduced, and there was no effect on the concentration of sulphadimidine (SDD), amoxicillin (AMO) and Diketo residues. Samples that exceeded the maximum residual limits (MRLs) were 17·0%, 12·0%, 10·0%, 16·0% and 14·0% for SDD, OTC, 4-Epi-OTC, AMO and Diketo, respectively. After boiling, no significant change was noted for SDD, AMO and Diketo, but all OTC and 4-Epi-OTC were completely below MRLs. Therefore, SDD and AMO with their metabolite (Diketo) are heat-stable antimicrobial residues with multiple human health hazards.

Both experimental hypo- and hyper-thyroidism exacerbate the adverse effects of chronic heat stress in broilers.

1. The effects of hypo- and hyper-thyroidism in mitigating or exacerbating the negative changes of chronic heat stress (HS) in broilers were investigated.2. Three-week-old broilers were distributed into six groups (n = 13 per group). Three groups were housed at ambient room temperature: control group (CN), propylthiouracil-treated group (AN) and thyroxine-treated group (TN). The other three groups were exposed to HS at 33 ± 1°C for 2 weeks: control heat stress (CH), propylthiouracil + heat stress (AH) and thyroxine + HS (TH).3. Induced hypothyroidy significantly decreased cloacal temperature and body weight gain in the birds in both the normal and HS groups (AN, AH). Conversely, hyperthyroidy resulted in a significant elevation in cloacal temperature in the TN and TH groups and a significant decline in weight gain in the TH group. Hyperthyroidy exacerbated the HS-induced degenerative changes in jejunal mucosa and caused noticeable vascular changes. A significant increase in the expression levels of jejunal nutrient transporter genes was observed in the AH and TH groups. The hyperthyroidic state significantly upregulated the HSP70 expression level in the TH group and the reverse occurred with propylthiouracil (PTU) treatment in the AH group.4. PTU supplementation to chicks reared under HS significantly decreased the triiodothyronine level, antibody (Ab) titre, and increased the heterophil-lymphocyte ratio. Furthermore, it induced higher hepatic glutathione peroxidase (GSH-Px) activity in the AN and AH groups and decreased the malondialdehyde content (MDA) in the AN group. Hyperthyroidy significantly increased triiodothyronine concentration, H/L ratio and decreased Hb concentration and Ab titres in the TH group. Additionally, this status increased the MDA content and decreased the GSH-Px activities.5. In conclusion, manipulation of thyroid status is not a remedy to overcome the undesirable effects of HS in broilers.

Insulin resistance associated with lower rates of weight gain in Pima Indians.

UNLABELLED: Insulin resistance is commonly associated with obesity and noninsulin-dependent diabetes. Whereas it predicts the development of diabetes, its effect on body weight change is unknown. We measured glucose disposal rates at submaximally- and maximally-stimulating insulin concentrations in 192 nondiabetic Pima Indians and followed their weight change over 3.5 +/- 1.8 y (mean +/- SD). RESULTS: (a) Insulin-resistant subjects gained less weight than insulin-sensitive subjects (3.1 vs. 7.6 kg, P less than 0.0001). (b) The percent weight change per year correlated with glucose disposal at submaximally-(r = 0.19, P less than 0.01) and maximally-stimulating (r = 0.34, P less than 0.0001) insulin concentrations independent of sex, age, initial weight, and 24-h energy expenditure; the correlations were stronger for glucose oxidation than for glucose storage. (c) Weight gain was associated with an increase in insulin resistance more than four times that predicted from the cross-sectional data. We conclude that insulin resistance is associated with a reduced risk of weight gain in nondiabetic Pima Indians.

MILK AS A SUBSTITUTE FOR SERUM IN DIAGNOSIS OF TOXOPLASMOSIS IN GOATS.

The present study determined the milk value rather than serum in diagnosis of toxoplasmosis in goats using ELISA and Modified Agglutination Test (MAT). ELISA proved to be more specific and sensitive (92% & 85%), than MAT (90% & 80%) in diagnosis of Anti-T. gondii Antibodies (ATAb) in group of microscopically proved T gondii aborted goats respectively. There was a direct relationship between.the mean ELISA O.D. value and the level of Ab-titer in MAT positive sera. The overall prevalence of infection in 600 serum samples from grazing goats was 22% and 20% after examination using ELISA and IAT respectively. It was lower after examination of their milk (20%) and (18%) by both techniques respectively. ATAb were significant high in serum (P < 0.05) during January, February and March, decreased significantly in April (P < 0.05) till August, then significant increased (P < 0.05) from September to December using ELISA. In time where ATAb were present by different levels among the whole year in serum, it didn't diagnose in milk from June to September. The infection was high in Egyptian Baladi breed in serum and milk (30% and 27%), while the Barki breed was the lowest one (13.33% and 12%) respectively. High rate of infection (30% in serum and 27% in milk) was recorded in goats > 2 years old, while no ATAb could be detected in goats less than one year old. The highest prevalence of infection (39.28% in serum and 37.14% in milk) was in Qalyoubia, the lowest one (11.25% & 9.58%) was in Giza governorate. The prevalence of infection was high after examination of serum and milk of goats with previous history of abortion in comparison with the other goats.

Insulin and hypertension. Relationship to obesity and glucose intolerance in Pima Indians.

The relationships among blood pressure, obesity, glucose tolerance, and serum insulin concentration were studied in 2873 Pima Indians aged 18-92 yr (mean 37 yr). Age- and sex-adjusted to the Pima population, the prevalence of hypertension (systolic blood pressure greater than or equal to 160 mmHg, diastolic blood pressure greater than or equal to 95 mmHg, or receiving drug treatment) was 7.1% for subjects with normal glucose tolerance compared with 13.0% for subjects with impaired glucose tolerance (IGT) and 19.8% for those with non-insulin-dependent diabetes mellitus (NIDDM) (P less than 0.001). The prevalence ratio of hypertension was 1.8 (95% confidence interval [CI] 1.2-2.5) for IGT and 2.6 (95% CI 2.0-3.2) for NIDDM compared with normal glucose tolerance, controlled for age, sex, and body mass index (BMI). In logistic regression analysis, hypertension was positively related to age, male sex, BMI, glucose tolerance, and fasting but not 2-h postload serum insulin concentration. Among subjects not taking antihypertensive drugs, however, neither fasting nor 2-h postload serum insulin was significantly related to hypertension. Furthermore, in 2033 subjects receiving neither antihypertensive nor antidiabetic drugs, blood pressure was not significantly correlated to fasting insulin concentration, and 2-h postload serum insulin was negatively correlated with diastolic blood pressure. In conclusion, insulin is not significantly related to blood pressure in Pima Indians not receiving antihypertensive drugs. Higher insulin concentrations in drug-treated hypertensive patients might result from the treatment rather than contribute to the pathogenesis of hypertension. Thus, these data do not support a major role for insulin in determining the occurrence of hypertension or regulation of blood pressure in Pima Indians.

Insulin treatment, endogenous insulin concentration, and ECG abnormalities in diabetic Pima Indians. Cross-sectional and prospective analyses.

The prevalence and incidence of CHD, defined by ECG abnormalities according to the Tecumseh criteria for Minnesota Codes, were determined in Pima Indians greater than or equal to 25 yr of age. In a cross-sectional analysis, the age-sex-adjusted prevalence (+/- SE) of ECG abnormalities was higher in 1454 NIDDM patients (6.86 +/- 0.65%) than in 1696 nondiabetic subjects (3.23 +/- 0.63%; prevalence rate ratio = 2.12; 95% CI 1.39-3.25). In a prospective analysis, the age-sex-adjusted incidence (+/- SE) of ECG abnormalities was higher in 824 NIDDM patients (12.77 +/- 1.67) than in 935 nondiabetic subjects (5.93 +/- 1.43 cases/1000 person-yr; incidence rate ratio = 2.15; 95% CI 1.26-3.69). The prevalence of ECG abnormalities in insulin-treated NIDDM patients was significantly higher than in NIDDM patients not treated with insulin (age-sex-adjusted OR = 2.83; 95% CI 1.84-4.33); and this association persisted when adjusted for other factors such as sBP, BMI, duration of diabetes, serum cholesterol concentration, and oral hypoglycemic agents (OR = 2.12; 95% CI 1.34-3.37). In the prospective analysis, the incidence of ECG abnormalities in NIDDM patients treated with insulin was higher than in those NIDDM patients not treated with insulin, but, when controlled for age, sex, duration of diabetes, and oral hypoglycemic agents in a proportional-hazards model, the relationship with insulin treatment was not statistically significant (incidence rate ratio = 1.36; 95% CI 0.80-2.31). This suggests that insulin treatment may be a marker of more severe diabetes, and that factors associated with clinical indications for insulin treatment, rather than insulin treatment per se, are related causally to CHD. On the other hand, endogenous fasting and 2-h postload serum insulin concentrations were not associated with ECG abnormalities among 761 NIDDM patients not treated with insulin nor among 1226 nondiabetic subjects. Furthermore, in the prospective study, neither endogenous fasting nor 2-h postload serum insulin was associated with the subsequent development of ECG abnormalities in NIDDM patients or nondiabetic subjects.

Abnormal glucose tolerance during pregnancy in Pima Indian women. Long-term effects on offspring.

The long-term effects on offspring of abnormal glucose tolerance detected during pregnancy were examined in 552 Pima Indian offspring 5-24 yr of age. Fasting hyperinsulinemia, presumably reflecting increased insulin resistance, occurred at an earlier age in the offspring of women who had abnormal glucose tolerance during pregnancy, and these offspring were more obese and had higher rates of abnormal glucose tolerance. When confounding factors were controlled, a 1 mM higher 2-h postload glucose concentration during pregnancy resulted in a significantly higher prevalence of diabetes in the offspring (odds ratio = 162). Maternal 2-h glucose concentration during pregnancy was also a significant predictor of glucose concentration during pregnancy in the offspring (P = 0.011). Thus, the metabolic abnormalities associated with the diabetic pregnancy result in long-term effects on the offspring, including insulin resistance, obesity, and diabetes, which in turn may contribute to transmission of risk for developing the same problems in the next generation.

Differences between the tolbutamide-boosted and the insulin-modified minimal model protocols.

The insulin-modified frequently sampled intravenous glucose tolerance test (FSIGTT) with minimal model analysis (MINMOD) was compared with the tolbutamide protocol and the glucose clamp in 35 nondiabetic subjects (age 38 +/- 2 years [mean +/- SE], BMI 27.2 +/- 0.9 kg/m2). Each subject underwent two FSIGTTs, one with tolbutamide (300 mg) and the other with insulin (0.03 U/kg) and a euglycemic hyperinsulinemic clamp (40 mU x m(-2) x min(-1)). Insulin sensitivity was determined from each FSIGTT with MINMOD and from the clamp. Insulin sensitivity indexes (S(I)) from the two FSIGTTs were significantly correlated (r = 0.77, P < 0.001), but S(I(insulin)) was 29 +/- 4% lower than S(I(tolbutamide)). Both S(I(insulin)) and S(I(tolbutamide)) correlated significantly with S(I(clamp)) (r = 0.70 and 0.71, P < 0.001 for each). Expressed in the same units (dl/min per pU/ml), S(I(tolbutamide)) was on average 13 +/- 6% lower than S(I(clamp)) (4.51 +/- 0.40 vs. 5.36 +/- 0.36 x 10(-2), P = 0.009), whereas S(I(insulin)) was 44 +/- 4% lower. S(G(tolbutamide)) and S(G(insulin)) were not different (1.88 +/- 0.10 vs. 2.01 +/- 0.09 x 10(-2) min(-1), P = 0.167) and were significantly correlated (r = 0.50, P = 0.002). Thus, insulin sensitivity estimates from both protocols correlate significantly with each other and with the clamp. They are quantitatively discrepant, however, possibly due to differences in the route of insulin delivery, saturation of insulin action, and/or tolbutamide-induced proinsulin release. Data obtained from these two MINMOD protocols are not directly comparable, and the same protocol must be used in any single cross-sectional or longitudinal study.

Insulin sensitivity and acute insulin response in African-Americans, non-Hispanic whites, and Hispanics with NIDDM: the Insulin Resistance Atherosclerosis Study.

NIDDM is usually characterized by beta-cell failure and decreased insulin sensitivity. It has been reported that a high proportion of African-American NIDDM subjects are insulin sensitive. To examine this issue, we determined insulin sensitivity (S(I)) in 479 NIDDM subjects by minimal model analyses of frequently sampled intravenous glucose tolerance (FSIGT) from the Insulin Resistance Atherosclerosis Study (IRAS), a large multicenter study of insulin sensitivity and cardiovascular risk in African-Americans, Hispanics, and non-Hispanic whites. The African-Americans and non-Hispanic whites were sampled in Los Angeles and Oakland, California. The non-Hispanic whites and Hispanics were sampled in San Antonio, Texas, and San Luis Valley, Colorado. We defined the proportion of insulin-sensitive (S(I)) subjects as > or =1.61 min-1 x microU-1 x ml-1, which is above the median for nondiabetic subjects of all ethnic groups in the IRAS. Using this definition, the proportion of insulin-sensitive diabetic subjects was very low in all ethnic groups (non-Hispanic whites [14.3%] vs. African-Americans [6.5%], P = 0.039 in Los Angeles and Oakland; non-Hispanic whites [6.8%] vs. Hispanics [4.9%], P = 0.737 in San Luis Valley and San Antonio). These results were also similar in newly diagnosed mildly hyperglycemic diabetic subjects. In addition, these results were not affected by the adjustment for differences in obesity, body fat distribution, and severity of hyperglycemia. Even in nonobese subjects (with BMI <30 kg/m2), the proportion of insulin-sensitive subjects (S(I) > or =1.61 min-1 x microU-1 x ml-1) was low (3.6-9.7%). The acute insulin response (AIR) was significantly higher in African-Americans than in non-Hispanic whites; there were no ethnic differences in AIR between Hispanics and non-Hispanic whites. There were no significant ethnic differences for non-insulin-mediated glucose disposal (S(G)). We conclude that the number of insulin-sensitive NIDDM subjects is low and similar among non-Hispanic whites, Hispanics, and African-Americans in the U.S.

Insulin sensitivity and abdominal obesity in African-American, Hispanic, and non-Hispanic white men and women. The Insulin Resistance and Atherosclerosis Study.

Increased abdominal obesity has been related to lower insulin sensitivity (SI), independent of overall obesity, but it has been suggested that this relationship may be weaker in non-whites. In the Insulin Resistance and Atherosclerosis Study (IRAS), SI was estimated using a minimal model analysis of the frequently sampled intravenous glucose tolerance test in 1,625 men and women aged 40-69 years. Subjects included African-Americans, Hispanics, and non-Hispanic whites from Oakland and Los Angeles, CA, San Antonio, TX, and the San Luis Valley, CO. Minimum waist circumference was significantly (P = 0.0001) associated with SI after adjusting for age, sex, height, BMI, glucose tolerance status, ethnicity, and clinic. This relationship was significantly (P = 0.0001) stronger in subjects with normal glucose tolerance (NGT) (beta = -0.030, P = 0.0001) than in those with impaired glucose tolerance (IGT) (beta = -0.010, P = 0.02; NIDDM: beta = -0.013, P = 0.0001). There were no significant ethnic differences in effect size across the spectrum of glucose tolerance. Waist circumference was also positively related to fasting insulin, an indirect measure of insulin sensitivity, in NGT (P = 0.0001), IGT (P = 0.0003), and NIDDM (P = 0.0002). The waist-fasting insulin relationship was significantly weaker in African-Americans, relative to non-Hispanic whites, in NGT and IGT (tests of statistical interaction: P = 0.04 and P = 0.02, respectively). In general, these patterns were similar in models specifying waist-to-hip ratio (WHR), rather than waist circumference, as the independent variable. While some ethnic variability exists, a negative relationship between abdominal obesity and insulin sensitivity was confirmed for all three ethnic groups across the spectrum of glucose tolerance.

Method of insulin administration has no effect on insulin sensitivity estimates from the insulin-modified minimal model protocol.

The effect of the method of insulin administration on insulin sensitivity estimates from the insulin modified minimal model (MINMOD) protocol was evaluated using the tolbutamide-boosted protocol as a reference. The study included 21 nondiabetic men ages 40 +/- 2 years (mean +/- SE) with a BMI of 26.6 +/- 1.1 kg/m2. Each subject underwent four frequently sampled intravenous glucose tolerance tests (FSIGTT), one with tolbutamide and three with the same insulin dosage (0.03 U/kg) given as a bolus or infusion over 5 or 10 min. The insulin sensitivity index (SI) of each subject was calculated from each FSIGTT with MINMOD. Insulin sensitivity indexes from the four FSIGTTs were highly correlated (r > 0.85, P < 0.001). SI(insulin) from the bolus and the 5- and 10-min infusion protocols were similar, but were 21 +/- 5, 29 +/- 5, and 23 +/- 4% lower than SI(tolbutamide), respectively. SG(tolbutamide) and SG(insulin) were not different among the four protocols and were significantly correlated (r > 0.55, P < 0.01). Thus the tolbutamide and insulin protocols must not be used interchangeably in any single cross-sectional or longitudinal study. When the same insulin dosage is used, the method of its administration has no bearing on insulin sensitivity estimates from the insulin-modified FSIGTT. The same method of insulin administration should be used, however, in any single study for purpose of standardization.

Increased insulin resistance and insulin secretion in nondiabetic African-Americans and Hispanics compared with non-Hispanic whites. The Insulin Resistance Atherosclerosis Study.

The etiology of NIDDM is still controversial, with both insulin resistance and decreased insulin secretion postulated as potential important factors. African-Americans and Hispanics have a two- to threefold excess risk of developing NIDDM compared with non-Hispanic whites. Yet little is known concerning the prevalence of insulin resistance and secretion defects in minorities, especially in African-Americans in population-based studies. Fasting and 2-h post-glucose load glucose and insulin levels, insulin-mediated glucose disposal (insulin sensitivity index) (S(I)), glucose effectiveness (S(G)), and first-phase insulin response (acute insulin response [AIR]) were determined in nondiabetic African-Americans (n= 288), Hispanics (n= 363), and non-Hispanic whites (n= 435) as part of the Insulin Resistance Atherosclerosis Study. Subjects received a standard 2-h oral glucose tolerance test on the first day and an insulin-modified frequently sampled intravenous glucose tolerance test on the second day. African-Americans and Hispanics were more obese than non-Hispanic whites. Both African-Americans and Hispanics had higher fasting and 2-h insulin concentrations and AIR but lower S(I) than non-Hispanic whites. No ethnic difference was observed in S(G). After further adjustments for obesity, body fat distribution, and behavioral factors, African-Americans continued to have higher fasting and 2-h insulin levels and AIR, but lower S(I) than non-Hispanic whites. In contrast, after adjustment for these covariates, no significant ethnic differences in S(I) or fasting insulin levels were observed between Hispanics and non-Hispanic whites. Hispanics continued to have higher 2-h insulin levels and AIRs than those in non-Hispanic whites. In this report, the association between S(I) and upper body adiposity (waist-to-hip, ratio) was similar in each ethnic group. Both nondiabetic African-Americans and Hispanics have increased insulin resistance and higher AIR than nondiabetic non-Hispanic whites, suggesting that greater insulin resistance may be in large part responsible for the higher prevalence of NIDDM in these minority groups. However, in Hispanics. the greater insulin resistance may be due to greater adiposity and other behavioral factors.

Physiological insulinemia acutely modulates plasma leptin.

Whether insulin acutely regulates plasma leptin in humans is controversial. We examined the dosage-response and time-course characteristics of the effect of insulin on leptin in 10 men (age 42+/-2 years [mean+/-SE]; BMI 29.3+/-2.0 kg/m2). Each individual underwent four 9-h euglycemic clamps (insulin at 20, 40, 80, and 400 mU x m[-2] x min[-1) and a control saline infusion. Although plasma glucose and insulin levels remained constant, leptin diminished from 9.1+/-3.0 to 5.9+/-2.1 ng/ml (P < 0.001) by the end of the control experiment. Conversely, plasma leptin showed a dosage-dependent increase during the insulin infusions that was evident within 30-60 min. The insulin-induced increase in leptin was proportionately lower in obese insulin-resistant men. Free fatty acids (FFAs) decreased during insulin and did not change during saline infusions. ED50 (the dose producing half-maximal effect) for insulin's effect on leptin and FFA was similar (138+/-36 vs. 102+/-24 pmol/l, respectively; P=0.11). To further define the role of physiological insulinemia, we compared the effect of a very low dosage insulin infusion (10 mU x m[-2] x min[-1]) with that of a control saline infusion in another group of 10 men (mean age 39+/-3 years; BMI 27.1+/-1.0 kg/m2). Plasma leptin remained stable during that insulin infusion, but fell by 37+/-2% in the control experiment. Thus physiological insulinemia can acutely regulate plasma leptin. Insulin could mediate the effect of caloric intake on leptin and could be a determinant of its plasma concentration. Inadequate insulin-induced leptin production in obese and insulin-resistant subjects may contribute to the development or worsening of obesity.

A comparison between the minimal model and the glucose clamp in the assessment of insulin sensitivity across the spectrum of glucose tolerance. Insulin Resistance Atherosclerosis Study.

An insulin-modified frequently sampled intravenous glucose tolerance test (FSIGTT) with minimal model analysis was compared with the glucose clamp in 11 subjects with normal glucose tolerance (NGT), 20 with impaired glucose tolerance (IGT), and 24 with non-insulin-dependent diabetes mellitus (NIDDM). The insulin sensitivity index (SI) was calculated from FSIGTT using 22- and 12-sample protocols (SI(22) and SI(12), respectively). Insulin sensitivity from the clamp was expressed as SI(clamp) and SIP(clamp). Minimal model parameters were similar when calculated with SI(22) and SI(12). SI could not be distinguished from 0 in approximately 50% of diabetic patients with either protocol. SI(22) correlated significantly with SI(clamp) in the whole group (r = 0.62), and in the NGT (r = 0.53), IGT (r = 0.48), and NIDDM (r = 0.41) groups (P < 0.05 for each). SI(12) correlated significantly with SI(clamp) in the whole group (r = 0.55, P < 0.001) and in the NGT (r = 0.53, P = 0.046) and IGT (r = 0.58, P = 0.008) but not NIDDM (r = 0.30, P = 0.085) groups. When SI(22), SI(clamp), and SIP(clamp) were expressed in the same units, SI(22) was 66 +/- 5% (mean +/- SE) and 50 +/- 8% lower than SI(clamp) and SIP(clamp), respectively. Thus, minimal model analysis of the insulin-modified FSIGTT provides estimates of insulin sensitivity that correlate significantly with those from the glucose clamp. The correlation was weaker, however, in NIDDM. The insulin-modified FSIGTT can be used as a simple test for assessment of insulin sensitivity in population studies involving nondiabetic subjects. Additional studies are needed before using this test routinely in patients with NIDDM.

Assessment of risk of overt nephropathy in diabetic patients from albumin excretion in untimed urine specimens.

The ability of an albumin-to-creatinine ratio, measured in a single untimed urine specimen, to indicate the likelihood of developing overt diabetic nephropathy was determined in 439 Pima Indians (134 men, 305 women) aged 25 years or older with non-insulin-dependent diabetes. During a mean follow-up period of 4.2 years, 59 (13%) of the subjects developed overt nephropathy, 47 (80%) of whom had albumin-to-creatinine ratios of 30 mg/g or greater at baseline. Subjects with albumin-to-creatinine ratios of 30 to 299 mg/g (a level of excretion often termed "microalbuminuria") had 9.2 times (95% confidence interval, 4.4 to 21.4) the incidence of overt nephropathy of those with ratios of less than 30 mg/g. Furthermore, the albumin-to-creatinine ratio remained a strong predictor of overt nephropathy even when controlled for age, sex, diabetes duration, mean blood pressure, and 2-hour postload plasma glucose concentration with a proportional-hazards function analysis. Thus, an albumin-to-creatinine ratio measured in a single untimed urine specimen is an effective means of identifying diabetic subjects who are at risk of developing overt nephropathy that could replace the more traditional timed urine collections.

Lipoprotein concentrations and carotid atherosclerosis by diabetes status: results from the Insulin Resistance Atherosclerosis Study.

OBJECTIVE: Lipoprotein concentrations are associated with the development of atherosclerosis in people with and without diabetes. The relative strength of these associations could differ by diabetes status as a result of diabetes-related lipoprotein modifications. RESEARCH DESIGN AND METHODS: The associations between lipoprotein concentrations and internal and common carotid artery intimal-medial thickness (IMT) assessed by B-mode ultrasonography were examined by diabetes status in a cross-sectional analysis among 1,391 participants in the Insulin Resistance Atherosclerosis Study. Participants included 442 individuals with type 2 diabetes, 308 with impaired glucose tolerance, and 641 with normal glucose tolerance. RESULTS: The differences in internal and common carotid IMT between the highest and lowest tertiles of LDL were 58.1 microm (P = 0.054) and 51.0 microm (P < 0.001), respectively. The differences in internal and common carotid IMT between the lowest and highest tertiles of HDL were 56.2 microm (P = 0.07) and 37.8 microm (P = 0.003), respectively Triglycerides and VLDL were not associated with IMT. These associations did not differ significantly because of diabetes status. CONCLUSIONS: These results support the importance of dyslipidemia as a major risk factor for atherosclerosis in people with diabetes. Future research in humans should measure lipoprotein oxidizability, glycation, size, and composition directly in people of differing glucose tolerance status to address the importance of diabetes-related lipoprotein modifications more conclusively.

Determinants of diabetes mellitus in the Pima Indians.

OBJECTIVE: To review the research findings on the determinants of diabetes mellitus in Pima Indians. RESEARCH DESIGN AND METHODS: Pima Indians in Arizona have participated in a longitudinal diabetes study that has provided data on and hypotheses about the development of NIDDM. Findings from this study are reviewed and updated. RESULTS: Frequency distributions of plasma glucose and HbA1 are bimodal in Pima adults, and substantial risk of the specific vascular complications of diabetes is confined to those in the higher components of these distributions. These findings contributed to the adoption of internationally recognized criteria for classification of glucose tolerance. Diabetes in the Pimas is strongly familial, and probably of genetic origin, although the precise nature of the gene or genes involved remains unknown. Obesity, which is at least in part environmentally determined, is a major factor interacting with the presumed genetic susceptibility to result in diabetes. The incidence of diabetes in the Pimas has increased during the last several decades, providing further evidence for environmental-genetic interaction. Longitudinal studies suggest that the progression from normal to diabetes can be considered to involve two stages. The first, primarily attributable to insulin resistance, leads to impaired glucose tolerance, and the second, which depends on insulin secretory failure, leads to worsening hyperglycemia and overt diabetes. CONCLUSIONS: The Pimas and many other American Indian populations suffer from a high incidence of diabetes and its characteristic disabling or fatal complications, and would benefit from continued research on the pathogenesis and prevention of the disease.

Diabetes and obesity in the offspring of Pima Indian women with diabetes during pregnancy.

OBJECTIVE: To review the long-term effects of the diabetic pregnancy on the offspring among the Pima Indians of Arizona. RESEARCH DESIGN AND METHODS: Studies published by the Phoenix Epidemiology and Clinical Research branch of the National Institute of Diabetes and Digestive and Kidney Diseases, since the inception of the longitudinal diabetes studies in 1965 were reviewed. In addition, pertinent studies from other centers, mentioned as references in these publications, were reviewed. As far as possible, all original articles and abstracts on this aspect of the Pima Indian studies were discussed. RESULTS: The offspring of women who had diabetes during pregnancy, on average, were more obese and had higher glucose concentrations and more diabetes than the offspring of women who developed diabetes after pregnancy or who remained nondiabetic. Although no new analyses were attempted, several of the older publications were updated by repeating the analyses on later, expanded data sets. CONCLUSIONS: The diabetic pregnancy, in addition to its effects on the newborn, has effects on the subsequent growth and glucose metabolism of the offspring. These effects are in addition to genetically determined traits.

Diabetic kidney disease in Pima Indians.

OBJECTIVE--To describe the natural history of kidney disease in Pima Indians with NIDDM. RESEARCH DESIGN AND METHODS--Review of previous studies describing diabetic kidney disease in this Native-American population and in other populations. RESULTS--NIDDM is the leading cause of renal failure in Pima Indians, among whom the incidence of ESRD is 23 times that of the general U.S. population. The high incidence of NIDDM and its early onset in the Pima undoubtedly contribute to this difference. The incidence of overt nephropathy and ESRD, as a function of diabetes duration, is at least as high in Pima Indians with NIDDM as that reported in other populations with IDDM. Furthermore, nearly all of the excess mortality associated with NIDDM is found in individuals with overt nephropathy. Mild elevations of UAE, which may be present even shortly after the onset of diabetes, predict the development of overt nephropathy in diabetic Pimas. Additional predictors include high blood pressure, level of glycemia, duration of diabetes, family history of diabetic nephropathy, and type of diabetes treatment. CONCLUSIONS--Diabetic kidney disease is a major cause of morbidity and mortality in Pima Indians. The natural history of diabetic kidney disease in this population is similar, in many ways, to the natural history described in individuals with IDDM.