Glucocorticoid-induced hyperglycaemia in respiratory disease: a systematic review and meta-analysis.

The relative risk of glucocorticoid-induced hyperglycaemia is poorly quantified. We undertook a meta-analysis to estimate the association between glucocorticoid treatment and hyperglycaemia, overall and separately in individuals with and without diabetes and underlying respiratory disease. We searched electronic databases for clinical trials of adults randomized to either glucocorticoid treatment or placebo. Eight articles comprising 2121 participants were identified. We performed a random effects meta-analysis to determine relative risks for the associations between glucocorticoid use and both hyperglycaemia and starting hypoglycaemic therapy. In all individuals, the relative risk of hyperglycaemia comparing glucocorticoid treatment with placebo was 1.72 [95% confidence interval (CI) 1.50-2.04; p < .001]. The relative risks in individuals with and those without diabetes were 2.10 (95% CI 0.92-5.02; p = .079) and 1.50 (95% CI 0.79-2.86; p = .22), respectively. In all individuals, the relative risk of hyperglycaemia requiring initiation of hypoglycaemic therapy, comparing glucocorticoid treatment with placebo, was 1.73 (95% CI 1.40-2.14; p < .001). In conclusion, glucocorticoid therapy increases the risk of hyperglycaemia in all individuals with underlying respiratory disease but not when diabetic status is analysed separately.

Diabetes mellitus in Kabuki syndrome 1 on a background of post-transplant diabetes mellitus.

Summary: Kabuki syndrome is a genetic disorder characterised by distinctive facial features, developmental delays, and multisystem congenital anomalies. Endocrine complications such as premature thelarche and short stature are common, whereas disorders of glycaemic control are less frequent. We describe a 23-year-old white female referred to the diabetes clinic for hyperglycaemia during haemodialysis. She was subsequently diagnosed with Kabuki syndrome based on characteristic clinical features, confirmed by detecting a heterozygous pathogenic variant in KMT2D. She was known to have had multiple congenital anomalies at birth, including complex congenital heart disease and a single dysplastic ectopic kidney, and received a cadaveric transplanted kidney at the age of 13. She had hyperglycaemia consistent with post-transplant diabetes mellitus (DM) and was started on insulin. Examination at the time revealed truncal obesity. She developed acute graft rejection and graft failure 14 months post-transplant and she was started on haemodialysis. Her blood glucose levels normalised post-graft explant, but she was hyperglycaemic again during haemodialysis at the age of 23. Given her clinical phenotype, negative diabetes antibodies and normal pancreas on ultrasound, she was assumed to have type 2 DM and achieved good glycaemic control with gliclazide. Learning points: Involve clinical genetics early in the investigative pathway of sick neonates born with multiple congenital anomalies to establish a diagnosis to direct medical care. Consider the possibility of Kabuki syndrome (KS) in the differential diagnoses in any neonate with normal karyotyping or microarray analysis and with multiple congenital anomalies (especially cardiac, renal, or skeletal), dysmorphic facial features, transient neonatal hypoglycaemia and failure to thrive. Consider the possibility of diabetes as an endocrine complication in KS patients who are obese or who have autoimmune disorders.

Smoking and other factors associated with short-term partial remission of Type 1 diabetes in adults.

AIMS: The duration of partial remission of Type 1 diabetes is associated with the degree of initial metabolic disturbance and features of insulin resistance. Cigarette smoking decreases insulin sensitivity, but its influence on the length of remission is unknown. Therefore, this study assessed the relationship between cigarette smoking and duration of partial remission in adults with newly diagnosed Type 1 diabetes. METHODS: We recruited 149 patients (48 women and 101 men, aged 16-35 years, median age 25 years), admitted to a teaching hospital with newly diagnosed Type 1 diabetes and followed them for a median period of 1 year and 9 months. We introduced intensive insulin therapy in multiple injections (basal-bolus) in all patients. We defined partial remission as an insulin dose of ≤ 0.3 U/kg body weight/24 h, an HbA(1c) value < 53 mmol/mol (7.0%) and a random serum C-peptide concentration over 0.5 ng/ml. Cigarette smoking was determined by self-report. RESULTS: Of 149 patients, 68 (46%) fulfilled the criteria for partial remission at 1 year after diagnosis of diabetes. Fewer patients who were in partial remission at 1 year smoked (19/68, 28%) than did patients that were not in partial remission (41/81, 51%). In logistic regression analyses, non-smoking was associated with remission at 1 year independent of age, sex, HbA(1c) and presence of diabetic ketoacidosis, all measured at onset of diabetes (OR 3.32, 95% CI 1.42-7.75, P = 0.005). CONCLUSION: Relative to individuals in this study who smoked, those who did not smoke at diagnosis of Type 1 diabetes experienced a longer duration of partial remission.

Maternal waist to hip ratio is a risk factor for macrosomia.

OBJECTIVE: Fetal growth during pregnancy may be affected by the metabolic activity and distribution of fat stores in women. This study investigates the association between waist to hip ratio (WHR) as a measure of the distribution of adiposity in primiparous mothers living in Avon, England, and macrosomia in their offspring. DESIGN: Prospective historical cohort study. SETTING: The Avon Longitudinal Study of Parents and Children (ALSPAC) prospective cohort study in Avon, UK. POPULATION: A cohort of 3083 primiparous women with a term singleton delivery with expected dates of delivery from 1 April 1991 to 31 December 1992. METHODS: The distribution of WHR was categorised into quartiles. We compared the second, third and fourth quartiles against the first (reference) quartile with respect to whether the mother delivered a macrosomic newborn. We controlled for maternal age, gestational age, body mass index (BMI), marital status and racial group using multivariate logistic regression. MAIN OUTCOME MEASURES: Macrosomia defined in three ways: birthweight ≥ 4000 g; birthweight ≥ 4500 g; large for gestational age (LGA: ≥ 95th percentile of birth weight adjusted for sex and gestational age). RESULTS: Waist to hip ratios in the third and fourth quartiles were associated with a higher odds of delivering a macrosomic infant, defined as a birthweight ≥ 4000 g (third quartile, OR 1.59, 95% CI 1.12-2.26; fourth quartile, OR 1.69, 95% CI 1.18-2.42) or as LGA (≥95th percentile of the cohort; third quartile, OR 1.77, 95% CI 1.10-2.85; fourth quartile, OR 1.78, 95% CI 1.09-2.91). When defined as a birthweight ≥ 4500 g, the fourth quartile was associated with increased odds of macrosomia (OR 2.74, 95% CI 1.05-7.16). Odds ratios after adjustment for confounding factors followed a similar pattern. CONCLUSION: Independent of confounding factors, women with increased WHRs were significantly more likely to give birth to macrosomic newborns.

Association between glycated haemoglobin and the risk of lower extremity amputation in patients with diabetes mellitus-review and meta-analysis.

AIMS/HYPOTHESIS: Diabetes increases the risk of lower extremity amputation (LEA). Although epidemiological studies report positive associations between glycaemia and LEA, the magnitude of the risk is not adequately quantified and clinical trials to date have not provided conclusive evidence about glucose lowering and LEA risk. We synthesised the available prospective epidemiological data on the association between glycaemia measured by HbA(1c) and the risk of LEA in individuals with diabetes. METHODS: We searched electronic databases and reference lists of relevant articles. We considered prospective epidemiological studies that had measured HbA(1c) level and assessed LEA as an outcome among diabetic individuals without acute foot ulcerations or previous history of amputation. Of 2,548 citations identified, we included 14 studies comprising 94,640 participants and 1,227 LEA cases. We abstracted data using standardised forms and obtained data from investigators when required. Data included characteristics of study populations, HbA(1c) assay methods, outcome and covariates. Study-specific relative risk estimates were pooled using random-effects model meta-analysis; heterogeneity was explored with meta-regression analyses. RESULTS: The overall RR for LEA was 1.26 (95% CI 1.16-1.36) for each percentage point increase in HbA(1c). There was considerable heterogeneity across studies (I (2) 76%, 67-86%; p < 0.001), which was not accounted for by recorded study characteristics. The estimated RR was 1.44 (95% CI 1.25-1.65) for type 2 diabetes and 1.18 (95% CI 1.02-1.38) for type 1 diabetes; however, the difference was not statistically significant (p = 0.09). We found no strong evidence for publication bias. CONCLUSIONS/INTERPRETATION: There is a substantial increase in risk of LEA associated with glycaemia in individuals with diabetes. In the absence of conclusive evidence from trials, this paper provides further epidemiological support for glucose-lowering as a strategy to reduce amputation in a population without acute foot ulceration or former amputation; it also provides disease modellers with estimates to assess the overall burden of hyperglycaemia.

Association between alcohol consumption and diabetic retinopathy and visual acuity-the AdRem Study.

AIMS: We investigated the association between alcohol consumption and diabetic retinopathy and deterioration of visual acuity in individuals with Type 2 diabetes. METHODS: We conducted a cohort analysis of 1239 participants with Type 2 diabetes aged 55-81 years enrolled in the AdRem study, a sub-study of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial. Current and past consumption of wine, spirits and beer was measured by self-report. Moderate and heavy alcohol consumption was defined as 1-14 and >14 drinks/week, respectively. Diabetic retinopathy, measured by mydriatic stereoscopic seven-field retinal photography, was defined by a 2-step progression in the Early Treatment of Diabetic Retinopathy Study (ETDRS) score or the presence of any retinal vascular lesions. Deterioration of visual acuity was defined by a decrease of two lines in best vision in either eye, measured corrected, or through a pinhole using a Snellen chart. RESULTS: In a mean follow-up of 5.5 years, we identified 182 participants with a 2-step progression in the ETDRS score, 640 participants with the presence of any retinal vascular lesions and 693 participants with a deterioration of visual acuity. Current moderate consumption of alcohol, compared with no current consumption, was not associated with presence or progression of diabetic retinopathy; however, it was associated with higher risk of deterioration of visual acuity (multivariable-adjusted OR 1.83; 95% CI 1.34-2.48; P<0.001). CONCLUSIONS: Alcohol consumption is associated with increased risk of deterioration of visual acuity, but not with retinopathy in individuals with Type 2 diabetes.

Association of C-reactive protein with type 2 diabetes: prospective analysis and meta-analysis.

AIMS/HYPOTHESIS: We examined the association between serum C-reactive protein (CRP) and incident diabetes in a prospective study, and added these data to a literature-based meta-analysis to explore potential sources of heterogeneity between studies. METHODS: We analysed a case-control study nested within the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort, including 293 incident diabetes cases and 708 controls. We combined 16 published studies on CRP and incident diabetes in a random-effect meta-analysis. RESULTS: In the EPIC-Norfolk cohort, serum CRP was associated with a higher risk of diabetes after adjusting for age, sex, BMI, family history of diabetes, smoking and physical activity (OR 1.49, comparing the extreme thirds of CRP distribution [95% CI 1.03-2.15], p = 0.03). However, the association was completely attenuated after further adjustment for WHR, serum gamma-glutamyltransferase and serum adiponectin (OR 1.00; 95% CI 0.66-1.51, p = 1.0). In a meta-analysis of 16 published studies with 3,920 incident diabetes cases and 24,914 controls, the RR was 1.72 (95% CI 1.54-1.92), comparing the extreme thirds of CRP distribution, with substantial heterogeneity between studies (I (2) = 52.8%, p = 0.007). CONCLUSIONS/INTERPRETATION: Initial evidence of association between CRP and incident diabetes was confounded by central adiposity, markers of liver dysfunction and adiponectin in the primary analysis. Despite an overall positive association in the meta-analysis, considerable heterogeneity existed between studies. The degree of adjustment for central adiposity and baseline glycaemia explained some of this heterogeneity and suggests that CRP may not be an independent risk factor for type 2 diabetes.

UKPDS-modelling of cardiovascular risk assessment and lifetime simulation of outcomes.

Although known principally as a clinical trial, the UK Prospective Diabetes Study (UKPDS) provided longitudinal data which helped define the natural history of cardiovascular complications in Type 2 diabetes. Using clinical, epidemiological, statistical and economics methods, UKPDS investigators developed mathematical models that helped define predictors (risk factors) for cardiovascular disease including angina, myocardial infarction, stroke, peripheral vascular disease and death in Type 2 diabetes. The UKPDS made clearer the contributions to risk of age, hyperglycaemia, elevated blood pressure, adverse blood lipids and smoking. Equations were developed, combined and incorporated into the UKPDS Risk Engine and the UKPDS Outcomes models. For example, the UKPDS risk engine-version 2-estimates that a white 62-year-old man with 11 years of Type 2 diabetes, a glycated haemoglobin of 8.3%, a systolic blood pressure of 145 mmHg and total and high-density lipoprotein cholesterol values of 5.8 and 1.1 mmol/l who did not smoke has a 33% chance of having overt coronary heart disease within 10 years. These models contribute to the estimation of risk and/or health outcomes adjusted for quality of life for use by, amongst others, clinicians, trialists, health planners, guideline developers and health economists.

Prevalence and projections of diabetes and pre-diabetes in adults in Sri Lanka--Sri Lanka Diabetes, Cardiovascular Study (SLDCS).

AIMS: To determine the prevalence of diabetes mellitus and pre-diabetes (impaired fasting glucose and impaired glucose tolerance) in adults in Sri Lanka. Projections for the year 2030 and factors associated with diabetes and pre-diabetes are also presented. METHODS: This cross-sectional study was conducted between 2005 and 2006. A nationally representative sample of 5000 adults aged >or= 18 years was selected by a multi-stage random cluster sampling technique. Fasting plasma glucose was tested in all participants and a 75-g oral glucose tolerance test was performed in non-diabetic subjects. Prevalence was estimated for those > 20 years of age. RESULTS: Response rate was 91% (n = 4532), males 40%, age 46.1 +/- 15.1 years (mean +/- standard deviation). The age-sex standardized prevalence (95% confidence interval) of diabetes for Sri Lankans aged >or= 20 years was 10.3% (9.4-11.2%) [males 9.8% (8.4-11.2%), females 10.9% (9.7-12.1%), P = 0.129). Thirty-six per cent (31.9-40.1%) of all diabetic subjects were previously undiagnosed. Diabetes prevalence was higher in the urban population compared with rural [16.4% (13.8-19.0%) vs. 8.7% (7.8-9.6%); P < 0.001]. The prevalence of overall, urban and rural pre-diabetes was 11.5% (10.5-12.5%), 13.6% (11.2-16.0%) and 11.0% (10.0-12.0%), respectively. Overall, 21.8% (20.5-23.1%) had some form of dysglycaemia. The projected diabetes prevalence for the year 2030 is 13.9%. Those with diabetes and pre-diabetes compared with normal glucose tolerance were older, physically inactive, frequently lived in urban areas and had a family history of diabetes. They had higher body mass index, waist circumference, waist-hip ratio, systolic/diastolic blood pressure, low-density lipoprotein cholesterol and triglycerides. Insulin was prescribed to 4.4% (2.7-6.1%) of all diabetic subjects. CONCLUSIONS: One in five adults in Sri Lanka has either diabetes or pre-diabetes and one-third of those with diabetes are undiagnosed.

Lower prevalence of impaired glucose tolerance and diabetes associated with daily seal oil or salmon consumption among Alaska Natives.

OBJECTIVE: To examine the association of seal oil and salmon consumption with impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) among Alaska Natives. RESEARCH DESIGN AND METHODS: Screening was performed on 666 Yup'ik Eskimos and Athabaskan Indians > or = 40 years old in 15 villages. Self-administered questionnaires were used to obtain partial food frequency data. A case was defined as IGT or NIDDM, either newly discovered or known. Newly discovered cases (11 patients with NIDDM and 17 with IGT) were determined by random blood glucose testing followed by a 2-h 75-g oral glucose tolerance test (OGTT) for those with values > or = 6.72 mmol/l or for subjects with unconfirmed histories of glucose intolerance. Known cases included 26 patients with NIDDM and 1 with IGT. Control subjects had random blood glucoses < 6.72 or normal OGTT results. RESULTS: Compared with less-than-daily consumption, both daily seal oil (odds ratio [OR] 0.2, 95% confidence interval [CI] 0.1-0.8) and daily salmon consumption (OR 0.5, CI 0.2-1.1) were associated with a lower prevalence of glucose intolerance, controlling for age, ethnicity, body mass index, and sex. The effects were similar when limited to newly discovered cases: OR 0.3, CI 0.1-1.3 for seal oil and OR 0.4, CI 0.1-1.3 for salmon. Consumption of seal oil at least five times per week was required to reduce risk. CONCLUSIONS: Consumption of seal oil and salmon, high in omega-3 fatty acids, appears to lower the risk of glucose intolerance and is a potentially modifiable risk factor for NIDDM in Alaska Natives.

Diabetes complications and mortality among Alaska Natives: 8 years of observation.

OBJECTIVE: To determine the prevalence and incidence of diabetes in Alaska Natives and the incidence of cerebrovascular accidents (stroke), myocardial infarction (MI), end-stage renal disease (ESRD), lower-extremity amputations (LEA), and mortality over a 6- to 8-year period. RESEARCH DESIGN AND METHODS: The data derive from a registry of diagnosed diabetes (World Health Organization [WHO] criteria) of the Alaska Area Native Health Service (AANHS), from medical records, and from the Alaska Bureau of Vital Statistics. RESULTS: From 1986 to 1993, the prevalence of diabetes in Alaska Natives increased by 22% from 15.7 to 19.2 per 1,000 people. Of these cases, nearly all were diagnosed with type II diabetes. During the same period, 614 new cases were diagnosed. The incidence was 1.5 per 1,000 Alaska Natives per year. The incidence of confirmed MI was 8.0 per 1,000 person-years of diabetes. Aleuts had the highest rate, followed by Indians and Eskimos. The incidence of confirmed stroke was 10.6 per 1,000 person-years of diabetes. Eskimos had a significantly higher rate than Indians (P = 0.002), and women had a higher rate than men. The incidence of LEA was 5.0 per 1,000 person-years of diabetes. The incidence rate dropped significantly after instituting a foot care program. The incidence for ESRD was 3.3 per 1,000 and also showed a decline with time. The all-cause mortality rate of 43.2 per 1,000 person-years of diabetes was nearly equal between men and women. Among Alaska Natives with diabetes, cardiovascular disease (CVD) was the most common cause of death, followed by cancer and diabetes, per se. CONCLUSIONS: We conclude that diabetes is increasing in Alaska Natives, who are experiencing both the microvascular and macrovascular complications of diabetes. The incidence of LEA and ESRD show some evidence of a decrease after intervention efforts.

Lower-extremity amputation in diabetes. The independent effects of peripheral vascular disease, sensory neuropathy, and foot ulcers.

OBJECTIVE: To identify risk factors for lower-extremity amputation (LEA) in individuals with diabetes and to estimate the incidence of LEA. RESEARCH DESIGN AND METHODS: This is a prospective study of 776 U.S. veterans in a general medicine clinic in Seattle, Washington. The outcome was first LEA during follow-up. Potential risk factors evaluated in proportional hazards models included, among others, peripheral vascular disease (PVD), sensory neuropathy, former LEA, foot deformities and ulcers, diabetes duration and treatment, and hyperglycemia. RESULTS: Associated with an increased risk for LEA were PVD defined as transcutaneous oxygen < or = 50 mmHg (relative risk [RR] = 3.0, 95% CI 1.3-7.1), insensitivity to monofilament testing (RR = 2.9, odds ratio = 1.1-7.8), lower-extremity ulcers (RR = 2.5, CI 1.1-5.4), former LEA, and treatment with insulin when controlling for duration of diabetes and other factors in the model. PVD defined as absent or diminished lower-extremity pulses or an ankle arm index < or = 0.8 was also associated with a significantly higher risk of LEA in separate models. Foot ulcers were associated with an increased ipsilateral risk of amputation. The age-adjusted incidence among men only for LEA standardized to the 1991 U.S. male diabetic population was 11.3/1,000 patient-years. CONCLUSIONS: This prospective study shows that peripheral sensory neuropathy, PVD, foot ulcers (particularly if they appear on the same side as the eventual LEA), former amputation, and treatment with insulin are independent risk factors for LEA in patients with diabetes.

Risk factors for diabetic peripheral sensory neuropathy. Results of the Seattle Prospective Diabetic Foot Study.

OBJECTIVE: To identify risk factors for diabetic lower-extremity peripheral sensory neuropathy prospectively in a cohort of U.S. veterans with diabetes. RESEARCH DESIGN AND METHODS: General medicine clinic outpatients with diabetes were followed prospectively for the development of insensitivity to the 5.07 monofilament on the foot. RESULTS: Of 775 subjects, 388 (50%) had neuropathy at baseline. Of the 387 subjects without neuropathy at baseline, 288 were followed up, and of these, 58 (20%) developed neuropathy. Multivariate logistic regression modeling of prevalent neuropathy controlling for sex and race revealed independent and significant associations with age, duration of diabetes, glycohemoglobin level, height, history of lower-extremity ulceration, callus, and edema; an independent and inverse correlation was noted with ankle-arm index. Risk factors for incident neuropathy in multivariate logistic regression included age, baseline glycohemoglobin level, height, history of ulcer, and CAGE screening instrument alcohol score; current smoking and albumin level were inversely associated with risk. CONCLUSIONS: Poorer glycemic control increases the risk of neuropathy and is amenable to intervention. Height and age directly increase risk of neuropathy and may help identify patients at risk. A proportion of neuropathy in diabetic veterans is probably due to or worsened by alcohol ingestion. Neuropathy was less common in current smokers than subjects not currently smoking.

Diabetes and impaired glucose tolerance in three Alaskan Eskimo populations. The Alaska-Siberia Project.

OBJECTIVE: The objectives of this study were to determine the prevalence of diabetes and impaired glucose tolerance (IGT) in three Alaskan Eskimo populations, using standardized diagnostic criteria, and to evaluate family history and obesity as risk factors. RESEARCH DESIGN AND METHODS: This cross-sectional study involved men and women > or = 25 years of age from three Eskimo ethnic groups (Siberian Yupik, Central Yupik, and Inupiat) residing in northwestern Alaska. Glucose tolerance status was defined by World Health Organization criteria and was based on a 75-g oral glucose tolerance test. Data on age, family history of diabetes, and degree of Eskimo ancestry were obtained from a personal interview. Obesity was assessed using BMI. RESULTS: A total of 454 of 899 (50.5%) eligible participants were examined for diabetic status (239 Siberian Yupik, 106 Central Yupik, and 109 Inupiat participants). The prevalence of diabetes was more than twice as high among the Siberian Yupik (9.6%) as among the Central Yupik (2.8%) and Inupiat participants (3.7%). Diabetes was more prevalent in women than men (8.8 vs. 4.2%). IGT was found in an additional 11.7% of the women and 4.7% of the men. The combined prevalence of diabetes and IGT in the population > or = 55 years of age was 30.4% (diabetes 12.0%, IGT 18.4%). Of the people identified with diabetes, 47% had not been previously diagnosed. Age-specific prevalences were similar to those found in U.S. whites in the National Health and Nutrition Examination Survey II. After adjustment for age, family history of diabetes was associated with diabetes in study participants with an odds ratio of 4.4, while obesity was associated with diabetes with an odds ratio of 2.6. CONCLUSIONS: These prevalences of diabetes are the highest yet reported among Eskimo populations. Obesity and family history of diabetes are associated with increased odds of developing diabetes. These data underscore the need to further examine risk factors and to design effective interventions.

Human furuncular myiasis caused by Hermetia illucens (Diptera: Stratiomyidae).

Cutaneous myiasis caused by Hermetia illucens (L.) has not been reported previously. We present a case of facultative furuncular myiasis characterized by infestation with a single larva in a woman from Seattle, WA, who had traveled to East Africa.

Cardiovascular risk reduction in diabetes: underemphasised and overdue. Messages from major trials.

Diabetes markedly increases the risk of coronary artery disease and death, but is underrecognised as a cardiovascular risk factor, despite the existence of effective treatments. Because patients with diabetes are at high risk for coronary disease, they have more to gain from prevention. There is evidence from clinical trials that select cardiovascular therapies may work better in diabetes, beyond their expected benefit, and may prevent diabetes itself.

Glucose tolerance and insulin-resistance syndrome among St. Lawrence Island Eskimos.

OBJECTIVES: Non-insulin-dependent diabetes mellitus (NIDDM) prevalence in Alaska Natives is rising but remains lower than the U.S. average. We conducted a screening study for diabetes mellitus and cardiovascular disease in a remote Yup'ik Eskimo community in Alaska. RESEARCH DESIGN AND METHODS: The study population included Siberian Yup'ik Eskimo residents of Gambell, Alaska, > or = age 40 years who underwent a 2 h 75 gm oral glucose tolerance test interpreted by WHO criteria. Other measurements included fasting serum insulin and lipid levels, bioimpedance body fat %, body-mass-index (BMI), waist-to-hip ratio (WHR), and blood pressure. RESULTS: Of 114 eligible subjects, 65 (57%) participated. These subjects had lower mean systolic or diastolic blood pressure, lower triglyceride, and higher mean HDL cholesterol levels compared to a similarly aged U.S. all races sample. The mean fasting insulin level of 50.9 pmol/L appeared low given the high mean BMI (27.2). Six subjects had NIDDM (9%, 95% CI 2%-16%) and eight had impaired glucose tolerance (IGT) (12%, 95% CI 4%-20%). Compared to normoglycemic subjects, diabetic subjects were more frequently female (83% vs 53%) and had higher mean systolic BP (138 mm Hg vs 117 mm Hg) than normoglycemic subjects. We used multiple regression to analyze associations between fasting insulin and either blood pressure or serum lipids, while adjusting for % body fat, WHR, age, sex, and antihypertensive medication use. Fasting insulin was significantly related to both diastolic blood pressure (p = .0430) and fasting serum triglyceride (p = .0182) but not to systolic BP, total cholesterol, or LDL and HDL subfractions. CONCLUSIONS: Although NIDDM prevalence was not high compared to non-Native U.S. residents, elements of the insulin-resistance syndrome exist in this subarctic population.

Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study.

OBJECTIVE: To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes. DESIGN: Prospective observational study. SETTING: 23 hospital based clinics in England, Scotland, and Northern Ireland. PARTICIPANTS: 4585 white, Asian Indian, and Afro-Caribbean UKPDS patients, whether randomised or not to treatment, were included in analyses of incidence; of these, 3642 were included in analyses of relative risk. OUTCOME MEASURES: Primary predefined aggregate clinical outcomes: any end point or deaths related to diabetes and all cause mortality. Secondary aggregate outcomes: myocardial infarction, stroke, amputation (including death from peripheral vascular disease), and microvascular disease (predominantly retinal photo-coagulation). Single end points: non-fatal heart failure and cataract extraction. Risk reduction associated with a 1% reduction in updated mean HbA(1c) adjusted for possible confounders at diagnosis of diabetes. RESULTS: The incidence of clinical complications was significantly associated with glycaemia. Each 1% reduction in updated mean HbA(1c) was associated with reductions in risk of 21% for any end point related to diabetes (95% confidence interval 17% to 24%, P<0.0001), 21% for deaths related to diabetes (15% to 27%, P<0.0001), 14% for myocardial infarction (8% to 21%, P<0.0001), and 37% for microvascular complications (33% to 41%, P<0.0001). No threshold of risk was observed for any end point. CONCLUSIONS: In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia. Any reduction in HbA(1c) is likely to reduce the risk of complications, with the lowest risk being in those with HbA(1c) values in the normal range (<6.0%).