DPD epitope-specific glutamic acid decarboxylase (GAD)65 autoantibodies in children with Type 1 diabetes.

AIM: To study whether DPD epitope-specific glutamate decarboxylase autoantibodies are found more frequently in children with milder forms of Type 1 diabetes. METHODS: We prospectively evaluated 75 children with new-onset autoimmune Type 1 diabetes, in whom we collected demographic, anthropometric and clinical data and measured islet autoantibodies. Glutamate decarboxylase 65 autoantibody-positive samples were analysed for epitope specificities using recombinant Fab against the DPD-defined epitope of glutamate decarboxylase 65. RESULTS: After adjustment for age, positive DPD epitope recognition was significantly associated with higher C-peptide levels at onset (P = 0.02, r2 =0.21, n = 35), and high DPD recognition in the highest quartile tended to be associated with HbA1c ≤ 53 mmol/mol (7%) at the last follow-up [mean (sd) follow-up 1.3 (0.4) years; P = 0.07; for the model, P = 0.044, n = 30)]. Age- and sex-adjusted BMI percentile was significantly correlated with recognition of the DPD-defined epitope (P < 0.03, r2 =0.14, n = 34), but this correlation was driven by the older age group (age ≥ 10 years; P = 0.016, r2 =0.27, n = 21) and was not significant in younger children (P = 0.93, n = 13). There were no independent associations with sex, race/ethnicity, diabetic ketoacidosis, HbA1c , HLA DR3-DQ2/DR4-DQ8 or autoantibody number. CONCLUSIONS: Our findings suggest that recognition of the DPD-defined glutamate decarboxylase 65 autoantibody epitope at Type 1 diabetes onset is directly associated with ß-cell function, BMI and age, which supports the hypothesis that immunological factors contribute to the clinical heterogeneity of Type 1 diabetes. Larger studies relating epitope-specific glutamate decarboxylase 65 autoantibody to clinical phenotype in children with Type 1 diabetes are warranted.

Viral mechanisms of adipose dysfunction: lessons from HIV-1 Vpr.

HIV-associated lipodystrophy is a heterogeneous, evolving condition associated with fundamental defects in adipose tissue differentiation, turnover and function. Although many antiretroviral drugs can affect adipose tissues adversely, clinical evidence suggests that factors associated with the virus per se could play a role. We have focused on the possibility that an HIV accessory protein, viral protein R (Vpr) could dysregulate metabolically critical transcription factors to cause the adipose dysfunction. In a recent study published in Science Translational Medicine, we utilized 2 animal models to show that Vpr, produced in tissues that sequester HIV after antiretroviral therapy, can act in a paracrine or endocrine fashion to disrupt adipocyte differentiation and function by inhibiting PPARγ target gene expression and activating glucocorticoid target gene expression. The phenotypic consequences included many features typical of the human syndrome, including accelerated lipolysis, increased macrophage infiltration in adipose tissue, diminished size of white adipose depots and hepatic steatosis. In this commentary, we summarize the background, results, and implications of these studies, and raise important questions for future investigation. More broadly, these studies suggest that chronic viral infections may be a causative factor in the pathogenesis of some forms of lipid metabolic disease, insulin resistance, and diabetes.

Serum adiposity-induced biomarkers in obese and lean children with recently diagnosed autoimmune type 1 diabetes.

BACKGROUND/OBJECTIVE: Obesity increases the risk of cardiovascular disease and diabetic complications in type 1 diabetes. Adipokines, which regulate obesity-induced inflammation, may contribute to this association. We compared serum adipokines and inflammatory cytokines in obese and lean children with new-onset autoimmune type 1 diabetes. SUBJECTS AND METHODS: We prospectively studied 32 lean and 18 obese children (age range: 2-18 yr) with new-onset autoimmune type 1 diabetes and followed them for up to 2 yr. Serum adipokines [leptin, total and high molecular weight (HMW) adiponectin, omentin, resistin, chemerin, visfatin], cytokines [interferon (IFN)-gamma, interleukin (IL)-10, IL-12, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha] and C-reactive protein (CRP) were measured at a median of 7 wk after diagnosis (range: 3-16 wk). RESULTS: Lean children were 71.9% non-Hispanic White, 21.9% Hispanic, and 6.3% African-American, compared with 27.8, 55.6, and 16.7%, respectively, for obese children (p = 0.01). Compared with lean children, obese children had significantly higher serum leptin, visfatin, chemerin, TNF-alpha and CRP, and lower total adiponectin and omentin after adjustment for race/ethnicity and Tanner stage. African-American race was independently associated with higher leptin among youth ≥10 yr (p = 0.007). Leptin levels at onset positively correlated with hemoglobin A1c after 1-2 yr (p = 0.0001) independently of body mass index, race/ethnicity, and diabetes duration. Higher TNF-alpha was associated with obesity and female gender, after adjustment for race/ethnicity (p = 0.0003). CONCLUSION: Obese children with new-onset autoimmune type 1 diabetes have a proinflammatory profile of circulating adipokines and cytokines that may contribute to the development of cardiovascular disease and diabetic complications.

Monitoring of oxidative stress in nurses occupationally exposed to antineoplastic drugs.

Antineoplastic drugs (ANDs) have been in clinical usage for more than five decades. The nonselective mechanism of action of ANDs between cancerous and noncancerous cells had well documented side effects such as acute symptoms, reproductive health issues, and potential cancer development in healthcare workers as a result of occupational exposure. The anticancer mechanism of ANDs is the generation of reactive oxygen species (ROS) which are responsible for various side effects in patients undergoing chemotherapy and the healthcare personnel occupationally exposed to them. ROS have potential to damage lipids, DNA, proteins, and so on leading to oxidative stress condition. The aim of this study was to evaluate the possible oxidative stress effect of antineoplastic drugs in nurses who routinely handle ANDs in an oncology hospital in south India. Malondialdehyde levels, reduced glutathione content, and glutathione S-transferase activity were analyzed in serum collected from 60 female nurses handling ANDs and compared with equal number of healthy volunteers matched by age and sex except AND exposure. The results showed statistically significant (P < 0.05) increase in malondialdehyde levels in the serum of exposed nurses. However, glutathione content and glutathione S-transferase activity was significantly decreased in these nurses. Our study suggests that the nurses occupationally exposed to ANDs were susceptible to the oxidative stress and emphasizes the need for a harmonized safe handling approach that assures minimal risk to the working nurses.

Oxidative stress induced by aluminum oxide nanomaterials after acute oral treatment in Wistar rats.

This study investigated the oxidative stress induced after acute oral treatment with 500, 1000 and 2000 mg kg⁻¹ doses of Al2O3 -30 and -40 nm and bulk Al2O3 in Wistar rats. Both the nanomaterials induced significant oxidative stress in a dose-dependent manner in comparison to the bulk. There was no significant difference between the two nanomaterials. However, the effect decreased with increase with time after treatment. The histopathological examination showed lesions only in liver with Al2O3 nanomaterials at 2000 mg kg⁻¹.

In vitro mutagenicity assessment of aluminium oxide nanomaterials using the Salmonella/microsome assay.

The aim of the current study was to evaluate the potential mutagenicity of aluminium oxide nanomaterials (NMs) (Al(2)O(3)-30 nm and Al(2)O(3)-40 nm). Characterization of the NMs was done before the initiation of the study. The mutagenicity of the NMs was studied by the Ames test with Salmonella typhimurium TA100, TA1535, TA98, TA97a and TA102 strains, in the presence and absence of the S9 mixture. Based on a preliminary cytotoxicity study conducted on the strains, different concentrations of Al(2)O(3)-30 nm, Al(2)O(3)-40 nm and Al(2)O(3)-bulk were selected. At all the concentrations tested, Al(2)O(3)-30 nm and Al(2)O(3)-40 nm did not significantly increase the number of revertant colonies compared to the Al(2)O(3)-bulk and control with or without S9 mixture. Our findings suggest that Al(2)O(3) NMs were devoid of any size and concentration dependent mutagenicity compared to the Al(2)O(3)-bulk and control.

Isolated sphenoid sinus disease - a retrospective analysis.

OBJECTIVE: To evaluate the etiology, symptoms, signs, imaging, surgical findings and outcomes of isolated sphenoid sinus disease (ISSD). DESIGN: Retrospective study. SETTINGS: Tertiary university based referral center. MATERIALS AND METHODS: All 8 patients aged 17-63, managed surgically in the department of ENT and Head and Neck Surgery at St. John's Medical College and Hospital, Bangalore from 2006 to 2008 for ISSD. Demographic data, presenting signs and symptoms endoscopic and imaging findings, surgical management, surgical pathology and clinical outcomes were investigated in the above patients. RESULTS: Of the 8 cases of ISSD, 5 were male; 3 were female, with an age range of 17-63 years. The most common presenting symptom was headache (7 patients [87.5%]), followed by nasal obstruction and recurrent URTI (5 cases [62.5%]). Imaging included CT and/or MRI studies in all cases. Sphenoid sinus pathology was varied and included 5 (62.5%) inflammatory cases, 1 (11.1%) cerebrospinal fluid fistula and 2 (22.2%) cases of sphenoid sinus neop;asms. Of the inflammatory cases 2 (40%) had isolated polyps in the sphenoid sinus [sphenochoanal polyps] and 3 (60%) had fungal sinusitis. Treatment was surgical, endoscopic transnasal sphenoidotomy under general anesthesia in all 5 patients with inflammatory ISSD Two patients with sphenoid sinus tumors underwent endoscopic biopsy. CONCLUSION: ISSD is rare. A high index of suspicion is required for diagnosis, which should be an active process and not one of exclusion. Both diagnostic nasal endoscopy and CT imaging are essential for diagnosis. The direct approach to the sphenoid sinus, transnasal endoscopic sphenoidotomy without ethmoidectomy is safe and effective. With early and adequate surgery we were able to avoid the morbidity associated with ISSD.

Intramuscular haemangioma of mylohyoid muscle: A case report.

OBJECTIVE: To report a case of intramuscular haemangioma (IMH) with a rare presentation in the mylohyoid, with emphasis on the clinical appearance, and histologic characteristics of the lesion. METHOD: Case report and review of the literature. CONCLUSION: Neck swellings can often present a diagnostic dilemma, with a wide preoperative differential diagnosis. IMH are rare benign haemangiomas occurring within the skeletal muscle. They account for approximately 1% of all haemangiomas. These are uncommon in the head and neck region and occur most frequently in the trunk and extremities. In the head and neck, masseter and trapezius are the most common sites involved. Intramuscular haemangioma is seldom diagnosed preoperatively, perhaps due to unfamiliarity with this uncommon lesion and nonspecific clinical findings.

Evaluation of genotoxic effects of oral exposure to aluminum oxide nanomaterials in rat bone marrow.

Nanomaterials have novel properties and functions because of their small size. The unique nature of nanomaterials may be associated with potentially toxic effects. The aim of this study was to evaluate the in vivo genotoxicity of rats exposed with Aluminum oxide nanomaterials. Hence in the present study, the genotoxicity of Aluminum oxide nanomaterials (30 and 40 nm) and its bulk material was studied in bone marrow of female Wistar rats using chromosomal aberration and micronucleus assays. The rats were administered orally with the doses of 500, 1000 and 2000 mg/kg bw. Statistically significant genotoxicity was observed with Aluminum oxide 30 and 40 nm with micronucleus as well as chromosomal aberration assays. Significantly (p < 0.05 or p < 0.001) increased frequency of MN was observed with 1000 and 2000 mg/kg bw dose levels of Aluminum oxide 30 nm (9.4 +/- 1.87 and 15.2 +/- 2.3, respectively) and Aluminum oxide 40 nm (8.1 +/- 1.8 and 13.9 +/- 2.21, respectively) over control (2.5 +/- 0.7) at 30 h. Likewise, at 48 h sampling time a significant (p < 0.05 or p < 0.001) increase in frequency of MN was evident at 1000 and 2000 mg/kg bw dose levels of Aluminum oxide 30 nm (10.6 +/- 1.68 and 16.6 +/- 2.66, respectively) and Aluminum oxide 40 nm (9.0 +/- 1.38 and 14.7 +/- 1.68, respectively) compared to control (1.8 +/- 0.75). Significantly increased frequencies (p < 0.05 or p < 0.001) of chromosomal aberrations were observed with Aluminum oxide 30 nm (1000 and 2000 mg/kg bw) and Aluminum oxide 40 nm (2000 mg/kg bw) in comparison to control at 18 and 24 h. Further, since there is need for information on the toxicokinetics of nanomaterials, determination of these properties of the nanomaterials was carried out in different tissues, urine and feces using inductively coupled plasma mass spectrometry (ICP-MS). A significant size dependent accumulation of Aluminum oxide nanomaterials occurred in different tissues, urine and feces of rats as shown by ICP-MS data. The results of our study suggest that exposure to Aluminum oxide nanomaterials has the potential to cause genetic damage.

In vivo assessment of genotoxic effects of Annona squamosa seed extract in rats.

Widespread use of pesticides represents a potential risk to human and environmental health. Hence, biopesticides from plants are some of the future strategies for plant protection. In this regard, a seed extract of Annona squamosa was prepared and found to be a promising pesticide. In order to establish the inherent toxicity and non-target safety required for registration and marketing of pesticides, toxicological studies are conducted. The genotoxicity potential was evaluated in rats with 75, 150 and 300 mg/kg Annona squamosa by the comet assay in leucocytes, micronucleus and chromosomal aberration tests in bone marrow. We also studied the effects of 300 mg/kg of extract on lipid peroxidation, reduced glutathione level and glutathione S transferase activity in liver, lungs, brain, kidneys, heart and spleen of treated rats. The comet assay showed a statistically significant dose related increase in DNA migration. The micronucleus and chromosomal aberration tests revealed a significant induction in frequency of micronuclei and chromosomal aberrations at 150 and 300 mg/kg. Annona squamosa treatment significantly enhanced lipid peroxidation, decreased glutathione and glutathione S transferase levels revealing the oxidative stress condition. Our results warrant careful use of Annona squamosa seed extract as a biopesticide till more tests are carried out.

In vivo genotoxicity assessment of aluminium oxide nanomaterials in rat peripheral blood cells using the comet assay and micronucleus test.

Advances in nanotechnology and its usage in various fields have led to the exposure of humans to engineered nanomaterials (NMs) and there is a need to tackle the potential human health effects before these materials are fully exploited. The main purpose of the current study was to assess whether aluminium oxide NMs (Al(2)O(3)-30 nm and Al(2)O(3)-40 nm) could cause potential genotoxic effects in vivo. Characterization of Al(2)O(3)-30 nm and Al(2)O(3)-40 nm was done with transmission electron microscopy, dynamic light scattering and laser Doppler velocimetry prior to their use in this study. The genotoxicity end points considered in this study were the frequency of micronuclei (MN) and the percentage of tail DNA (% Tail DNA) migration in rat peripheral blood cells using the micronucleus test (MNT) and the comet assay, respectively. Genotoxic effects were evaluated in groups of female Wistar rats (five per group) after single doses of 500, 1000 and 2000 mg/kg body weight (bw) of Al(2)O(3)-30 nm, Al(2)O(3)-40 nm and Al(2)O(3)-bulk. Al(2)O(3)-30 nm and Al(2)O(3)-40 nm showed a statistically significant dose-related increase in % Tail DNA for Al(2)O(3)-30 nm and Al(2)O(3)-40 nm (P < 0.05). However, Al(2)O(3)-bulk did not induce statistically significant changes over control values. The MNT also revealed a statistically significant (P < 0.05) dose-dependent increase in the frequency of MN, whereas Al(2)O(3)-bulk did not show any significant increase in frequency of MN compared to control. Cyclophosphamide (40 mg/kg bw) used as a positive control showed statistically significant (P < 0.001) increase in % Tail DNA and frequency of MN. The biodistribution of Al(2)O(3)-30 nm and Al(2)O(3)-40 nm and Al(2)O(3)-bulk in different rat tissues, urine and feces was also studied 14 days after treatment using inductively coupled plasma mass spectrometry. The data indicated that tissue distribution of Al(2)O(3) was size dependent. Our findings suggest that Al(2)O(3) NMs were able to cause size- and dose-dependent genotoxicity in vivo compared to Al(2)O(3)-bulk and control groups.

Effect of a lifestyle intervention on change in cardiorespiratory fitness in adults with type 2 diabetes: results from the Look AHEAD Study.

OBJECTIVE: To examine the effect of an intensive lifestyle weight loss intervention (ILI) compared to diabetes support and education (DSE) on changes in fitness and physical activity in the Look AHEAD trial. DESIGN: Randomized clinical trial to compare a lifestyle intervention for weight loss with a DSE condition in individuals with type 2 diabetes. SUBJECTS: Data from 4376 overweight or obese adults with type 2 diabetes (age=58.7+/-6.8 years, body mass index (BMI)=35.8+/-5.8 kg/m(2)) who completed 1 year of the Look AHEAD trial and had available fitness data were analyzed. INTERVENTION: Subjects were randomly assigned to DSE or ILI. DSE received standard care plus three education sessions over the 1-year period. ILI included individual and group contact throughout the year, restriction in energy intake and 175 min per week of prescribed physical activity. MEASUREMENTS: Fitness was assessed using a submaximal graded exercise test. Physical activity was assessed by questionnaire in a subset of 2221 subjects. RESULTS: Change in fitness was statistically greater in ILI vs DSE after adjustment for baseline fitness (20.9 vs 5.7%; P<0.0001). Multivariate analysis showed that change in fitness was greater in overweight vs obese Class II and III (P<0.05). Physical activity increased by 892+/-1694 kcal per week in ILI vs 108+/-1254 kcal per week in DSE (P<0.01). Changes in fitness (r=0.41) and physical activity (r=0.42) were significantly correlated with weight loss (P<0.0001). CONCLUSIONS: The ILI was effective in increasing physical activity and improving cardiorespiratory fitness in overweight and obese individuals with type 2 diabetes. This effect may add to weight loss in improving metabolic control in patients in lifestyle intervention programs.

Predictors of glycaemic control in indigent patients presenting with diabetic ketoacidosis.

AIM: To derive predictors of good glycaemic control in patients presenting with diabetic ketoacidosis (DKA) followed prospectively in a specialized clinic. METHODS: One hundred and sixty-one adult patients were admitted during a 31-month period and followed for at least 12 months. After 1 year, the patients were classified into three groups: good control (GC) (HbA1c < or = 7%), intermediate control (IC) (HbA1c 7-9%) and poor control (PC) (HbA1c > 9%). Characteristics of patients in the three groups were compared both at baseline and during follow-up. RESULTS: At 12 months, 36% of the patients were classified as GC, 27% as IC and 37% as PC. GC patients had higher fasting serum C-peptide levels 0.7 +/- 0.54 compared to 0.38 +/- 0.29 and 0.16 +/- 0.21 nmol/l, respectively, for the IC and PC patients (p < 0.0001). A higher proportion GC patient had a C-peptide level greater than 0.33 nmol/l than that for IC and PC patients (86, 61 and 19%, respectively; p < 0.0001). Exogenous insulin was safely discontinued in 50, 30 and 3% of patients, respectively, in the GC, IC and PC groups (p < 0.0001). Compliance with life-style interventions was higher in the GC than that in IC and PC patients (87, 41 and 5%, respectively; p < 0.0001). In the logistic regression analysis, predictors of good glycaemic control were having baseline fasting serum C-peptide value > or =0.33 mmol/l, OR: 3.01 (95% CI 1.07-8.55, p = 0.03) and compliance with life-style interventions OR 12.66 (95% CI 3.73-51.57, p = 0.0001). CONCLUSION: Among adult patients with DKA, significant predictors of good glycaemic control are preserved beta-cell function and compliance with life-style modifications.

Factors associated with insulin discontinuation in subjects with ketosis-prone diabetes but preserved beta-cell function.

AIM: To evaluate factors predictive of insulin discontinuation in subjects with ketosis-prone Type 2 diabetes. METHODS: One hundred and six subjects with ketosis-prone Type 2 diabetes were recruited during the index episode of diabetic ketoacidosis (DKA). All subjects were followed in a special clinic for at least 6 months. If the subject's glycaemic control reached specified glycaemic goals, exogenous insulin was gradually decreased until discontinuation. Baseline and follow-up characteristics were compared between the off-insulin and the on-insulin groups. RESULTS: At the end of the follow-up period (915+/-375 days) insulin was discontinued in 47% subjects. Subjects in the off-insulin group were significantly older at the time of diagnosis of diabetes. In the off-insulin group the majority of subjects were newly diagnosed with diabetes. After 6 months of follow-up, subjects in the off-insulin group had significantly lower mean HbA(1c), higher mean C-peptide-to-glucose ratio and had more clinic visits per year. In the proportional hazard analysis, new-onset diabetes [hazard ratio (HR) 1.54; 95% confidence interval (CI) 1.02-2.45], and a higher C-peptide-to-glucose ratio at 6 months of follow-up (HR 1.77; 95% CI 1.22-2.63) were significant predictors of insulin discontinuation. CONCLUSIONS: In subjects with ketosis-prone Type 2 diabetes, the best predictors of insulin discontinuation are having new-onset diabetes, and higher beta-cell functional reserve (as measured by the C-peptide-to-glucose ratio).

Weight loss in obese Mexican Americans treated for 1-year with orlistat and lifestyle modification.

OBJECTIVE: To evaluate the effectiveness of a culturally appropriate lifestyle intervention combined with orlistat in producing weight loss with obese Mexican-American women. SUBJECTS: Mexican-American women (N=108), aged 21-65 y, with a body mass index (BMI) > or =27 kg/m(2) were randomized to 1 y of treatment with orlistat and a culturally tailored lifestyle modification intervention (OLM; n=56) or a wait-list control group (WLC; n=52). DESIGN: A randomized, controlled, open-label 12-month study. Orlistat was dosed at 120 mg, three times per day. The OLM intervention included behavior modification, a low-fat (< or =30% of total daily calories) diet, and moderate physical activity (> or =150 min/week). MEASUREMENT: Primary outcomes included changes in body weight (kg), BMI, waist circumference, blood pressure, glucose, and lipids. RESULTS: A total of 72 (37 OLM, 35 WLC) and 66 participants (32 OLM, 34 WLC) completed the 6- and 12-month follow-ups, respectively. Repeated-measures ANOVA demonstrated a significant time x treatment interaction (Wilks' lambda=12.61; P<0.001), indicating that OLM-treated patients achieved significant weight loss relative to the WLC group during the study (mean percentage weight loss+/-s.e.m.; -8.1%+/-1.2 vs -1.6%+/-0.7 at 6 months and -8.8%+/-1.5 vs -0.2%+/-1.0 at 12 months, respectively). OLM-treated patients also experienced significant reductions in waist circumference, low-density-lipoprotein, and total cholesterol. CONCLUSIONS: This study demonstrates the effectiveness of an intervention combining orlistat and lifestyle modification with Mexican-American women, a population with substantial risk for obesity.

High frequency of serious infections in patients with panhypopituitarism: a case-control study.

We reviewed the records of 65 patients with panhypopituitarism (PHP) for the frequency and types of infections requiring hospitalization, and documented serious infections in 13 of 65 patients with PHP. The increased frequency of serious infectious diseases in patients with PHP is likely to contribute to increased age-specific mortality.

Myotonic dystrophy protein kinase (DMPK) induces actin cytoskeletal reorganization and apoptotic-like blebbing in lens cells.

DMPK, the product of the DM locus, is a member of the same family of serine-threonine protein kinases as the Rho-associated enzymes. In DM, membrane inclusions accumulate in lens fiber cells producing cataracts. Overexpression of DMPK in cultured lens epithelial cells led to apoptotic-like blebbing of the plasma membrane and reorganization of the actin cytoskeleton. Enzymatically active DMPK was necessary for both effects; inactive mutant DMPK protein did not produce either effect. Active RhoA but not constitutive GDP-state mutant protein produced similar effects as DMPK. The similar actions of DMPK and RhoA suggest that they may function in the same regulatory network. The observed effects of DMPK may be relevant to the removal of membrane organelles during normal lens differentiation and the retention of intracellular membranes in DM lenses.

Ethnicity affects the postprandial regulation of glycogenolysis.

We investigated the effect of nutrient intake on glucose metabolism in normal Mexican-Americans (n = 6) and European-Americans (n = 6). Subjects were studied after an 18-h fast and after 5-6 h of ingestion of hourly meals that supplied 6.35 or 12.75 micromol glucose. kg(-1). min(-1). Endogenous glucose production (EGP), gluconeogenesis (GNG), and glycogenolysis (GLY) were estimated by mass isotopomer analysis with [U-(13)C]glucose infusions. Fasting EGP, GNG, and GLY did not differ between the groups. Food ingestion lowered the molar rate of GNG by only 31%. However, while consuming the lower quantity of nutrients, Mexican-Americans had higher plasma glucose (P < 0.05), a 39% higher rate of EGP (P < 0.05), and a 68% (P < 0.025) higher rate of GLY than the European-Americans. At the higher intake, EGP and GLY were suppressed completely in both groups. There was a linear relationship between insulin concentrations, EGP, and GLY in both groups, but the slope of the line was significantly (P < 0.05) greater in the European-Americans. We conclude that the sensitivity of GLY to nutrient intake differs between ethnic groups and that this may play a role in the increased predisposition of Mexican-Americans to type II diabetes.

New profiles of diabetic ketoacidosis: type 1 vs type 2 diabetes and the effect of ethnicity.

BACKGROUND: Diabetic ketoacidosis (DKA) has been reported to occur in type 2 diabetes, but the frequency and distinguishing features of this syndrome remain to be defined. We determined the "diabetic types," ethnic distributions, and phenotypes of patients with DKA in an urban hospital. METHODS: We reviewed the hospital admissions and followed the clinical course of adults who developed DKA. We classified patients as "type 1," "type 2," or "new onset" based on their treatment history. New-onset patients were reassessed 2 1/2 years or more after the episode of DKA and classified as "type 1" or "type 2" based on insulin requirements. We compared the groups for ethnic distributions and clinical features. RESULTS: Of 141 patients, 55 (39%) who presented with DKA had type 2 diabetes, while 75 (53%) had type 1 diabetes and 11 (8%) could not be "typed." Hispanics mainly had type 2 and whites predominantly had type 1, while African Americans had a slight preponderance of type 1 diabetes (P=.001). Type 1 patients were mainly lean, while the body mass indexes (BMIs) (calculated as the weight in kilograms divided by the square of height in meters) of type 2 patients were bimodally distributed (33% with BMI<25 and 51% with BMI>30; P<.001). Age of onset of diabetes was predominantly younger than 40 years in the type 1 group but was more broadly distributed in the type 2 group (P<.001). Ninety-three percent of the new-onset patients who were reassessed had type 2 diabetes. Half of the type 2 patients had no identifiable stress factor associated with the episode of DKA. CONCLUSIONS: A high proportion of DKA in nonwhite adults occurs in persons with type 2 diabetes, especially in those with previously undiagnosed diabetes. The frequency and clinical heterogeneity of this syndrome in a multiethnic population have significant implications for the diagnosis, classification, and management of adults with diabetes.