Common variants in genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1/2), adiponectin concentrations, and diabetes incidence in the Diabetes Prevention Program.

AIMS: Baseline adiponectin concentrations predict incident Type 2 diabetes mellitus in the Diabetes Prevention Program. We tested the hypothesis that common variants in the genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1, ADIPOR2) would associate with circulating adiponectin concentrations and/or with diabetes incidence in the Diabetes Prevention Program population. METHODS: Seventy-seven tagging single-nucleotide polymorphisms (SNPs) in ADIPOQ (24), ADIPOR1 (22) and ADIPOR2 (31) were genotyped. Associations of SNPs with baseline adiponectin concentrations were evaluated using linear modelling. Associations of SNPs with diabetes incidence were evaluated using Cox proportional hazards modelling. RESULTS: Thirteen of 24 ADIPOQ SNPs were significantly associated with baseline adiponectin concentrations. Multivariable analysis including these 13 SNPs revealed strong independent contributions of rs17366568, rs1648707, rs17373414 and rs1403696 with adiponectin concentrations. However, no ADIPOQ SNPs were directly associated with diabetes incidence. Two ADIPOR1 SNPs (rs1342387 and rs12733285) were associated with ∼18% increased diabetes incidence for carriers of the minor allele without differences across treatment groups, and without any relationship with adiponectin concentrations. CONCLUSIONS: ADIPOQ SNPs are significantly associated with adiponectin concentrations in the Diabetes Prevention Program cohort. This observation extends prior observations from unselected populations of European descent into a broader multi-ethnic population, and confirms the relevance of these variants in an obese/dysglycaemic population. Despite the robust relationship between adiponectin concentrations and diabetes risk in this cohort, variants in ADIPOQ that relate to adiponectin concentrations do not relate to diabetes risk in this population. ADIPOR1 variants exerted significant effects on diabetes risk distinct from any effect of adiponectin concentrations.

Association of the SLC30A8 missense polymorphism R325W with proinsulin levels at baseline and after lifestyle, metformin or troglitazone intervention in the Diabetes Prevention Program.

AIMS/HYPOTHESIS: Individuals with impaired glucose tolerance have increased proinsulin levels, despite normal glucose or C-peptide levels. In the Diabetes Prevention Program (DPP), increased proinsulin levels predicted type 2 diabetes and proinsulin levels were significantly reduced following treatment with metformin, lifestyle modification or troglitazone compared with placebo. Genetic and physiological studies suggest a role for the zinc transporter gene SLC30A8 in diabetes risk, possibly through effects on insulin-processing in beta cells. We hypothesised that the risk allele at the type 2 diabetes-associated missense polymorphism rs13266634 (R325W) in SLC30A8 would predict proinsulin levels in individuals at risk of type 2 diabetes and may modulate response to preventive interventions. METHODS: We genotyped rs13266634 in 3,007 DPP participants and examined its association with fasting proinsulin and fasting insulin at baseline and at 1 year post-intervention. RESULTS: We found that increasing dosage of the C risk allele at SLC30A8 rs13266634 was significantly associated with higher proinsulin levels at baseline (p = 0.002) after adjustment for baseline insulin. This supports the hypothesis that risk alleles at SLC30A8 mark individuals with insulin-processing defects. At the 1 year analysis, proinsulin levels decreased significantly in all groups receiving active intervention and were no longer associated with SLC30A8 genotype (p = 0.86) after adjustment for insulin at baseline and 1 year. We found no genotype × treatment interactions at 1 year. CONCLUSIONS/INTERPRETATION: In prediabetic individuals, genotype at SLC30A8 predicts baseline proinsulin levels independently of insulin levels, but does not predict proinsulin levels after amelioration of insulin sensitivity at 1 year.

Assessing gene-treatment interactions at the FTO and INSIG2 loci on obesity-related traits in the Diabetes Prevention Program.

AIMS/HYPOTHESIS: The single nucleotide polymorphism (SNP) rs9939609 in the fat mass and obesity associated gene (FTO) and the rs7566605 SNP located 10 kb upstream of the insulin-induced gene 2 gene (INSIG2) have been proposed as risk factors for common obesity. METHODS: We tested for genotype-treatment interactions on changes in obesity-related traits in the Diabetes Prevention Program (DPP). The DPP is a randomised controlled trial of 3,548 high-risk individuals from 27 participating centres throughout the USA who were originally randomised to receive metformin, troglitazone, intensive lifestyle modification or placebo to prevent the development of type 2 diabetes. Measures of adiposity from computed tomography were available in a subsample (n = 908). This report focuses on the baseline and 1 year results. RESULTS: The minor A allele at FTO rs9939609 was positively associated with baseline BMI (p = 0.003), but not with baseline adiposity or the change at 1 year in any anthropometric trait. For the INSIG2 rs7566605 genotype, the minor C allele was associated with more subcutaneous adiposity (second and third lumbar vertebrae [L2/3]) at baseline (p = 0.04). During follow-up, CC homozygotes lost more weight than G allele carriers (p = 0.009). In an additive model, we observed nominally significant gene-lifestyle interactions on weight change (p = 0.02) and subcutaneous (L2/3 [p = 0.01] and L4/5 [p = 0.03]) and visceral (L2/3 [p = 0.02]) adipose areas. No statistical evidence of association with physical activity energy expenditure or energy intake was observed for either genotype. CONCLUSIONS/INTERPRETATION: Within the DPP study population, common variants in FTO and INSIG2 are nominally associated with quantitative measures of obesity, directly and possibly by interacting with metformin or lifestyle intervention.

Testing of diabetes-associated WFS1 polymorphisms in the Diabetes Prevention Program.

AIMS/HYPOTHESIS: Wolfram syndrome (diabetes insipidus, diabetes mellitus, optic atrophy and deafness) is caused by mutations in the WFS1 gene. Recently, single nucleotide polymorphisms (SNPs) in WFS1 have been reproducibly associated with type 2 diabetes. We therefore examined the effects of these variants on diabetes incidence and response to interventions in the Diabetes Prevention Program (DPP), in which a lifestyle intervention or metformin treatment was compared with placebo. METHODS: We genotyped the WFS1 SNPs rs10010131, rs752854 and rs734312 (H611R) in 3,548 DPP participants and performed Cox regression analysis using genotype, intervention and their interactions as predictors of diabetes incidence. We also evaluated the effect of these SNPs on insulin resistance and beta cell function at 1 year. RESULTS: Although none of the three SNPs was associated with diabetes incidence in the overall cohort, white homozygotes for the previously reported protective alleles appeared less likely to develop diabetes in the lifestyle arm. Examination of the publicly available Diabetes Genetics Initiative genome-wide association dataset revealed that rs10012946, which is in strong linkage disequilibrium with the three WFS1 SNPs (r(2)=0.88-1.0), was associated with type 2 diabetes (allelic odds ratio 0.85, 95% CI 0.75-0.97, p=0.026). In the DPP, we noted a trend towards increased insulin secretion in carriers of the protective variants, although for most SNPs this was seen as compensatory for the diminished insulin sensitivity. CONCLUSIONS/INTERPRETATION: The previously reported protective effect of select WFS1 alleles may be magnified by a lifestyle intervention. These variants appear to confer an improvement in beta cell function.

The Pro12Ala variant at the peroxisome proliferator-activated receptor gamma gene and change in obesity-related traits in the Diabetes Prevention Program.

AIMS/HYPOTHESIS: Peroxisome proliferator-activated receptor gamma (PPARgamma), encoded by the PPARG gene, regulates insulin sensitivity and adipogenesis, and may bind polyunsaturated fatty acids (PUFA) and thiazolidinediones in a ligand-dependent manner. The PPARG proline for alanine substitution at position 12 (Pro12Ala polymorphism) has been related with obesity directly and via interaction with PUFA. METHODS: We tested the effect-modifying role of Pro12Ala on the 1 year change in obesity-related traits in a randomised clinical trial of treatment with metformin (n = 989), troglitazone (n = 363) or lifestyle modification (n = 1,004) vs placebo (n = 1,000) for diabetes prevention in high-risk individuals. RESULTS: At baseline, Ala12 carriers had larger waists (p < 0.001) and, in a subset, more subcutaneous adipose tissue (SAT; lumbar 2/3; p = 0.04) than Pro12 homozygotes. There was a genotype-by-intervention interaction on 1-year weight change (p = 0.01); in the placebo arm, Pro12 homozygotes gained weight and Ala12 carriers lost weight (p = 0.001). In the metformin and lifestyle arms, weight loss occurred across genotypes, but was greatest in Ala12 carriers (p < 0.05). Troglitazone treatment induced weight gain, which tended to be greater in Ala12 carriers (p = 0.08). In the placebo group, SAT (lumbar 2/3, lumbar 4/5) decreased in Ala12 allele carriers, but was unchanged in Pro12 homozygotes (p < or = 0.005). With metformin treatment, SAT decreased independently of genotype. In the lifestyle arm, SAT (lumbar 2/3) reductions occurred across genotypes, but were greater in Ala12 carriers (p = 0.03). A genotype-by-PUFA intake interaction on reduction in visceral fat (lumbar 4/5; p = 0.04) was also observed, which was most evident with metformin treatment (p < 0.001). CONCLUSIONS/INTERPRETATION: Within the Diabetes Prevention Program, the Ala12 allele influences central obesity, an effect which may differ by treatment group and dietary PUFA intake (ClinicalTrials.gov ID no: NCT00004992).

Effects of glycaemic control on cardiovascular disease in diabetic American Indians: the Strong Heart Study.

AIMS: Diabetes increases the risk of cardiovascular disease (CVD). Only part of this excess risk is explained by diabetes-associated hypertension, obesity, and lipid disorders. Poor glycaemic control may help explain the residual CVD risk. The aim of this study was to determine whether variations in glycaemic control are associated with CVD risk in diabetic individuals. METHODS: We examined longitudinal data from the Strong Heart Study, a population-based study of CVD and its risk factors among American Indians (a population with a high prevalence of diabetes). Diabetes was defined using the 1998 World Health Organization criteria: fasting plasma glucose >/= 126 mg/dl or 2-h plasma glucose >/= 200 mg/dl. American Diabetes Association guidelines for glycaemic control were used: good, A(1c) < 7%; fair, 7-7.9%; and poor, >/= 8%. The analysis was based on data from diabetic individuals with no CVD at baseline. RESULTS: During 9 years of follow-up, 494 of the 2011 diabetic participants developed CVD. Although Cox multivariate regression modelling showed dose-response effects of glycaemic control on overall CVD and coronary heart disease (CHD) incidence, the relationships were weakened when adjusted for confounding variables. Kaplan-Meier analysis, however, showed that diabetic individuals with poor baseline glycaemic control had significantly increased proportions of overall CVD and CHD (P = 0.001) during the 9 years of follow-up, compared with those who had good or fair control. CONCLUSIONS: These findings highlight the importance of risk factors, such as high blood pressure and dyslipidaemia, in increasing CVD risk in those with diabetes.

The 2003 Carl A Moyer Award: real-time metabolic monitors, ischemia-reperfusion, titration endpoints, and ultraprecise burn resuscitation.

Real-time metabolic monitoring of varied vascular beds provides the raw data necessary to conduct ultraprecise burn shock resuscitation based on second-by-second assessment of regional tissue perfusion. It also illustrates shortcomings of current clinical practices. Arterial base deficit was continuously monitored during 11 clinical resuscitations of patients suffering burn shock using a Paratrend monitor. Separately, in a 30% TBSA rat burn model (N = 70), three Paratrend monitors simultaneously recorded arterial blood gas and tissue pCO2 of the burn wound and colonic mucosa during resuscitation at 0, 2, 4, 6, and 8 ml/kg/%TBSA. Paratrend data were analyzed in conjunction with previously reported laser Doppler images of actual burn wound capillary perfusion. With current clinical therapy, continuous monitoring of arterial base deficit revealed repetitive cycles of resolution/worsening/resolution during burn shock resuscitation. In the rat model, tissue pCO2 in both burn wounds and splanchnic circulation differed depending on the rate of fluid resuscitation (P <.01 between sham and 0 ml/kg/%TBSA and between 2 ml/kg/%TBSA and 4 ml/kg/%TBSA). Burn wound pCO2 values correlated well with laser Doppler determination of actual capillary perfusion (rho = -.48, P <.01). The following conclusions were reached: 1). Gratuitous and repetitive ischemia-reperfusion-ischemia cycles plague current clinical therapy as demonstrated by numerous "false starts" in the resolution of arterial base deficit; 2). in a rat model, real-time monitoring of burn wound and splanchnic pCO2 demonstrate a dose-response relationship with rate of fluid administration; and 3). burn wound and splanchnic pCO2 are highly correlated with direct measurement of burn wound capillary perfusion by laser Doppler imager. Either technique can serve as a resuscitation endpoint for real-time feedback-controlled ultraprecise resuscitation.

Digital photography: enhancing communication between burn therapists and nurses.

Burn rehabilitation therapists rely on nursing staff to follow through with the positioning and splinting programs. To communicate more effectively, a communication tool that consisted of digital photos and written instructions was created. Microsoft Word and Nikon View software were used to design the communication tool. The purpose of the study was to assess the perceived effectiveness of a communication tool between burn therapists and burn nurses for splinting and positioning. Thirty-two surveys were distributed to burn nursing staff to assess their perception of the communication tool (digital photographs with written instructions) compared with previous methods of instructions (without digital photographs). Seventy-three percent of nurses felt the communication tool with verbal instructions were the best methods of communicating splinting and positioning needs. All respondents felt that the rehabilitation staff should continue to use the communication tool.

Laser Doppler imaging determines need for excision and grafting in advance of clinical judgment: a prospective blinded trial.

INTRODUCTION: Clinicians' judgment as to which burns require excision and grafting remains one aspect of burn care without objective measurements. This study presents a prospective, blinded trial to assess decision to operate by laser Doppler imaging (numerical criteria) versus the clinical judgment of an experienced burn surgeon. METHODS: A number of 23 patients were enrolled in this prospective trial and 41 representative wounds of indeterminate depth were selected for observation. Daily determination of need to operate (burn depth) was made by a single burn surgeon. Laser Doppler imager (LDI) scans of the same wounds were simultaneously obtained, and not revealed to the clinician. Data analysis compared quickness of decision to operate by LDI to the clinician's judgment. Concurrence of decisions by either method was compared. RESULTS: A total of 23 patients and 41 wounds were analyzed. LDI and the surgeon agreed in determination of wound depth 56% of the time (23/41, P=0.031). Biopsy confirmation was obtained for 21 wounds. The surgeon's determination of burn depth was accurate in 71.4% of wounds biopsied (15/21). When the LDI scan median flux indicated need for excision, it was 100% accurate (7/7). When both the surgeon and the LDI were correct in assessing wound depth, LDI would have saved median number of 2 days (minimum=0, maximum=4). CONCLUSION: LDI allowed for earlier, objective determination of need to operate. Concurrence with clinical judgment in this blinded study was excellent. LDI should be seen as an effective aid to clinical judgment when contemplating excision of burns with indeterminate depth.

Microvascular assessment of burn depth conversion during varying resuscitation conditions.

Conversion of partial- to full-thickness injuries, even after the burning has stopped, remains a significant clinical problem. We developed a rat model with a wide range of burn depths to study this phenomenon by microvascular assessment. Fifty-four male Sprague-Dawley rats weighing 460 g on average were studied. Real-time tissue monitoring of pH, paCO2, and paO2 was achieved by placement of a continuous blood gas monitor transducer in the aorta. Ten, 2-cm x 2-cm burns were created on each animal with milled aluminum templates (100 degrees C) with varying contact times. Conversion of burn depth in these wounds was documented by serial laser Doppler imager scanning over a 5-hour period. Animals received Ringer's lactate resuscitation at 0, 2, 4, 6, and 8 ml/kg/%burn. Serial laser Doppler scanning directly demonstrated progressive loss of perfusion to partial-thickness burns dependent upon the amount of fluid resuscitation. Conversion of partial- to full-thickness burns in this rat model (documented by laser Doppler microvascular assessment) was dependent upon how the animals were resuscitated.

Percutaneous fibrin sheath stripping versus transcatheter urokinase infusion for malfunctioning well-positioned tunneled central venous dialysis catheters: a prospective, randomized trial.

PURPOSE: To compare central dialysis catheter patency rates after stripping procedures with those after urokinase (UK) infusion. MATERIALS AND METHODS: Fifty-seven tunneled catheters with either (i) flow rates less than 250 mL/min and established baseline flow rates > or = 300 mL/min or (ii) flow rates 50 mL/min less than higher established baseline flows were prospectively randomized to undergo stripping procedures (n = 28) or UK infusion (n = 29) at 30,000 U/h via each port concurrently, for a total 250,000 U. Success and patency were determined by dialysis at normal flow rates (> or = 300 mL/min) or at the previously established higher baseline rate. Flow rates were monitored weekly. Primary patency ended with catheter malfunction or removal. Kaplan-Meier survival analysis was used to construct survival curves. RESULTS: In the stripping group, initial clinical success was 89% (25 of 28). The 15-, 30-, and 45-day primary patency rates were 75% (n = 20), 52% (n = 13), and 35% (n = 8), respectively. The median duration of additional function was 32 days (95% CI: 18-48 d). In the UK group, initial clinical success was 97% (28 of 29). The 15-, 30-, and 45-day primary patency rates were 86% (n = 21), 63% (n = 13), and 48% (n = 9), respectively. The median duration of additional patency was 42 days (95% CI: 22-153 d). The Wilcoxon test for equality detected no significant difference in the survival curves for the two treatment groups (P = .236). CONCLUSION: There is no significant difference in time to primary patency between the two methods. Both allow temporary catheter salvage in most patients.

Effects of obesity and body fat distribution on lipids and lipoproteins in nondiabetic American Indians: The Strong Heart Study.

OBJECTIVES: To examine the relationship between obesity and lipoprotein profiles and compare the effects of total obesity and central adiposity on lipids/lipoproteins in American Indians. RESEARCH METHODS AND PROCEDURES: Participants were 773 nondiabetic American Indian women and 739 men aged 45 to 74 years participating in the Strong Heart Study. Total obesity was estimated using body mass index (BMI). Central obesity was measured as waist circumference. Lipoprotein measures included triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein AI (apoAI), and apolipoprotein B (apoB). Partial and canonical correlation analyses were used to examine the associations between obesity and lipids/ lipoproteins. RESULTS: Women were more obese than men in Arizona (median BMI 32.1 vs. 29.2 kg/m2) and South Dakota and North Dakota (28.3 vs. 28.0 kg/m2), but there was no sex difference in waist circumference. Men had higher apoB and lower apoAI levels than did women. In women, when adjusted for center, gender, and age, BMI was significantly related to HDL cholesterol (r = -0.24, p < 0.001). There was a significant but weak relation with apoAI (r = -0.14, p < 0.001). Waist circumference was positively related to triglycerides (r = 0.14, p < 0.001) and negatively related to HDL cholesterol (r = -0.23, p < 0.001) and apoAI (r = -0.13, p < 0.001). In men, BMI was positively correlated with triglycerides (r = 0.30, p < 0.001) and negatively correlated with HDL cholesterol (r = -0.35, p < 0.001) and apoAI (r = -0.23, p < 0.001). Triglycerides increased with waist circumference (r = 0.30, p < 0.001) and HDL cholesterol decreased with waist circumference (r = -0.36, p < 0.001). In both women and men there was an inverted U-shaped relationship between obesity and waist with LDL cholesterol and apoB. In canonical correlation analysis, waist circumference received a greater weight (0.86) than did BMI (0.17) in women. However, the canonical weights were similar for waist (0.46) and BMI (0.56) in men. Only HDL cholesterol (-1.02) carried greater weight in women, whereas in men, triglycerides (0.50), and HDL cholesterol (-0.64) carried a large amount of weight. All the correlation coefficients between BMI, waist circumference, and the first canonical variable of lipids/lipoproteins or between the individual lipid/lipoprotein variables and the first canonical variable of obesity were smaller in women than in men. Triglycerides and HDL cholesterol showed clinically meaningful changes with BMI and waist circumference in men. All lipid/lipoprotein changes in women in relation to BMI and waist circumference were minimal. DISCUSSION: The main lipoprotein abnormality related to obesity in American Indians was decreased HDL cholesterol, especially in men. Central adiposity was more associated with abnormal lipid/lipoprotein profiles than general obesity in women; both were equally important in men.

Relation of generalized and central obesity to cardiovascular risk factors and prevalent coronary heart disease in a sample of American Indians: the Strong Heart Study.

OBJECTIVE: To examine the hypothesis linking measures of obesity including body mass index (BMI), waist circumference (waist) and percentage body fat to coronary heart disease (CHD) prevalence and its risk factors in American Indians. DESIGN: The Strong Heart Study assesses the prevalence of CHD and its risk factors in American Indians in Arizona, Oklahoma and South/North Dakota. Participants underwent a physical examination and an electrocardiogram; anthropometric and blood pressure measurements were taken, as were measurements of glucose, lipoproteins, fibrinogen, insulin, hemoglobin A1c and urinary albumin. PARTICIPANTS: Data were available for 4549 men and women between 45 and 74 y of age. MEASUREMENTS: Obesity, measured using body mass index, waist circumference and percentage body fat, was correlated with prevalent CHD and its risk factors. RESULTS: More than 75% of participants were overweight (BMI>25 kg/m2). Measures of obesity were greater in women than in men, in younger than in older participants, and in participants with diabetes than in nondiabetic participants. CHD risk factors were associated with measures of obesity but, except for insulin concentration, changes in metabolic variables with increasing obesity were small. Associations were not stronger with waist than with BMI. The prevalence of CHD in those whose BMI and/or waist measurements lay in the lowest and highest quintiles, by gender and diabetic status, was similar. CONCLUSIONS: Although CHD risk factors are associated with obesity in American Indians, distribution of obesity (ie waist) is no more closely related to risk factors than is generalized obesity (ie BMI), and changes in CHD risk factors with obesity were small. Thus, the relations among obesity, body fat distribution and CHD risk may differ in this population.

Effect of physician specialty on outcomes in diabetic ketoacidosis.

OBJECTIVE: More than 100,000 people are hospitalized annually in the U.S. with diabetic ketoacidosis (DKA). Outcome differences have not been examined for these patients based on whether their primary care provider is a generalist or a diabetes specialist. The objective of this study was to investigate hospital charges and hospital length of stay (LOS) for patients with DKA according to the specialty of their primary care provider. RESEARCH DESIGN AND METHODS: We investigated all patients with a primary diagnosis of DKA during a 3.5-year period (n = 260) in a large urban teaching hospital. Hospital charges and LOS were studied regarding the specialty of the primary care provider. Demographic factors, severity of illness, laboratory data, and readmission rates were compared. RESULTS: Patients cared for by generalists and endocrinologists had a similar case mix and severity of DKA. The age-adjusted mean LOS for patients of generalists was 4.9 days (95% CI 4.5-5.4), and the mean LOS for patients of endocrinologists was 3.3 days (2.6-4.2) (P < 0.0043). Mean hospital charges differed (P < 0.0001) with an age- and sex-adjusted mean for patients of endocrinologists of $5,463 ($4,179-7,141) and a mean for patients of generalists of $10,109 ($9,151-11,166). The additional charges incurred by generalists were due in part to patients undergoing more procedures. No differences in diabetes-related complications occurred during admission, but the endocrinologist-treated group had a lower readmission rate for DKA during the study period than the generalist-treated group (2 vs. 6%, respectively) (P = 0.03). CONCLUSIONS: Endocrinologists provide more cost-effective care than generalists do when serving as primary care providers for patients hospitalized with DKA.

Glycemic control in diabetic American Indians. Longitudinal data from the Strong Heart Study.

OBJECTIVE: To describe glycemic control and identify correlates of elevated HbA1c levels in diabetic American Indians participating in the Strong Heart Study, which is a longitudinal study of cardiovascular disease in American Indians in Arizona, Oklahoma, South Dakota, and North Dakota. RESEARCH DESIGN AND METHODS: This analysis is based on data from the baseline (1989-1992) and first follow-up (1994-1995) examinations of the Strong Heart Study. The 1,581 diabetic participants included in this analysis were aged 45-74 years at baseline, were diagnosed with diabetes before and at baseline, and had their HbA1c levels measured at follow-up. HbA1c was used as the index of glycemic control. Characteristics that may affect glycemic control were evaluated for cross-sectional and longitudinal relationships by analysis of covariance and multiple regression. RESULTS: There was no significant difference between median HbA1c at baseline (8.4%) and at follow-up (8.5%). Sex, age (inversely), and insulin and oral hypoglycemic agent therapy were significantly related to HbA1c levels in both the cross-sectional and longitudinal analyses. Current smoking, prior use of alcohol, and duration of diabetes were significant only for the cross-sectional data. Baseline HbA1c significantly and positively predicted HbA1c levels at follow-up. Comparison of HbA1c by therapy type shows that insulin therapy produced a significant decrease in HbA1c between the baseline and follow-up examinations. CONCLUSIONS: Glycemic control was poor among diabetic American Indians participating in the Strong Heart Study. Women, patients taking insulin or oral hypoglycemic agents, and younger individuals had the worst control of all the participants. Baseline HbA1c, and weight loss predicted worsening of control, whereas insulin therapy predicted improvement in control. Additional therapies and/or approaches are needed to improve glycemic control in this population.

Intraoperative blood salvage in excisional burn surgery: an analysis of yield, bacteriology, and inflammatory mediators.

The diminution of intraoperative hemorrhage remains a fundamental goal of the burn surgeon. We hypothesized that intraoperative blood salvage during burn excisions would be feasible if predicated on yield, bacteriology, and concentration of inflammatory mediators in the washed product. Reinfusion of culture-positive blood has a clear precedent in the trauma literature. Eight operations with immediate and complete collection of shed blood into a cell-saver device were prospectively studied. A median salvage rate of 43% of total shed red blood cells was estimated to have been recovered. Actual volumetric measurement of intraoperative blood loss was achieved. Bacterial contamination was consonant with the abdominal trauma experience. The levels of C3a, C5a, TNF alpha, and IL-1 beta in the final cell-saver product were all found to be at clinically insignificant levels.

The relationship between weight and response to cholesterol-lowering diets in women.

OBJECTIVE: To determine whether factors related to body weight might influence the cholesterol lowering response to diet. DESIGN: Run-In diet followed by crossover to low fat diets; average response is reported. SUBJECTS: Sixty-three subjects (30 men and 33 women) with moderately elevated plasma cholesterol levels. MEASUREMENTS: Lipid and anthropometric measurements. Data were analyzed as a repeated measures analysis of variance with lipid lowering response in all combined cholesterol lowering diets compared to baseline. RESULTS: LDL cholesterol lowering was significantly affected by BMI in women (P = 0.01) but not in men (P = 0.54). There was also a weak effect of waist-hip (W/H) ratio on response (P = 0.127) in women, with the lower responders having a higher W/H ratio but there was no effect of W/H ratio in men (P = 0.86). CONCLUSION: These results suggest that overweight women with elevated plasma cholesterol may be less responsive to reducing their cholesterol levels with diet.

Polyunsaturated fatty acids result in greater cholesterol lowering and less triacylglycerol elevation than do monounsaturated fatty acids in a dose-response comparison in a multiracial study group.

Cholesterol-lowering effects of polyunsaturated and monounsaturated fatty acids were compared as they were varied in a reciprocal dose-dependent fashion in the context of a National Cholesterol Education Program (NCEP) Step 1 diet. The study population comprised 63 moderately hypercholesterolemic African American and white men and women. After a 6-wk baseline diet containing 37% of energy from total fat and 15% from saturated fat, participants consumed four diets for 6 wk each, in random order, containing 10% of energy as saturated fatty acids; 3%, 6%, 10%, and 14% of energy as polyunsaturated fatty acids; and 17%, 14%, 10%, and 6% of energy as monounsaturated fatty acids. Dietary cholesterol, fiber, plant sterol, and squalene contents were constant with all four diets. There was a progressive decrease in total (P = 0.028) and low-density-lipoprotein cholesterol (P = 0.184) across the four diets, with the greatest decrease observed in the diet with the highest content of polyunsaturated fatty acids; a small but significant decrease in high-density-lipoprotein (HDL) cholesterol that did not show a trend between the polyunsaturated and monounsaturated diets; and a trend between the four diets in triacylglycerol elevations (P = 0.029), with the smallest increment occurring in the diets highest in polyunsaturates. The magnitude of the cholesterol-lowering response was greater in those with higher baseline cholesterol and less in those who were more obese. The dietary response was similar in both ethnic groups and in both sexes. In conclusion, in an NCEP Step 1 diet containing 30% total fat, with all other known cholesterol-influencing dietary factors held constant, the substitution of polyunsaturated fatty acid for monounsaturated fatty acid from 3% to 14% resulted in a progressive decline in total cholesterol and less triacylglycerol elevations, without effect on HDL cholesterol.

Effects of sex and ethnicity on responses to a low-fat diet: a study of African Americans and whites.

The effects of sex and ethnicity on plasma lipoprotein changes that occur with low-fat diets were studied in 34 African American subjects (20 women, 14 men) and 29 white subjects (13 women, 16 men) aged 25-62 y with moderate hypercholesterolemia. A baseline diet containing 37% fat (15% saturated) was compared with four experimental diets containing 30% fat (10% saturated) with reciprocally varying contents of polyunsaturated and monounsaturated fatty acids. Diets were fed for 6 wk each, and all food and beverages provided and compliance were intensively monitored. Body weight and physical activity were held constant. Lowering of total and low-density-lipoprotein cholesterol were similar between women and men and between African Americans and whites. Small differences were observed between women and men in the extent of high-density lipoprotein lowering and triacylglycerol elevations. Additionally, African American subjects had slightly higher triacylglycerol elevations than did white subjects. Results suggest that men and women of varied ethnic backgrounds should respond similarly to cholesterol-lowering diets. Studies are required to develop strategies for achieving dietary changes that consider diverse eating patterns and cultural barriers to dietary adherence.