Harmonization of criteria and terminology in fetal rat skeletal evaluations.

BACKGROUND: A survey of laboratories in North American and Europe that routinely conduct fetal skeletal examinations was performed with the purpose of (1) understanding current terminology used for classifying skeletal findings in developmental toxicity (DT) studies and (2) understanding the criteria used to identify relatively common findings that sufficiently deviate from normal. The goal was to promote terminology harmonization and improve interlaboratory consistency in the criteria used to identify developmental anomalies. METHODS: The survey, designed based on terminology for developmental anomalies recommended by an international collaboration (Makris et al., Congenital Anomalies, 2009;49(3):123-246), was conducted by a subgroup (authors of this publication) of the Royal Society of Biology's International Register of Fetal Morphologists (IRFM). RESULTS: Individual and summarized anonymized responses are provided here. The authors, who are expert fetal morphologists with experience performing fetal examinations, reviewed the responses and generated recommendations on preferred terminology and criteria for determining when morphological variations deviate from normal and warrant recording of the findings for skeletal observations in Sprague Dawley (SD) fetal rats. The objective of these recommendations is to complement Makris et al. (Congenital Anomalies, 2009;49(3):123-246). CONCLUSION: The broad application will improve interlaboratory harmonization of recording fetal skeleton findings in developmental toxicity studies intended for regulatory submissions, including SEND (Standard for Exchange of Nonclinical Data).

2022 update to the position statement by Primary Care Diabetes Europe: a disease state approach to the pharmacological management of type 2 diabetes in primary care.

Type 2 diabetes and its associated comorbidities are growing more prevalent, and the complexity of optimising glycaemic control is increasing, especially on the frontlines of patient care. In many countries, most patients with type 2 diabetes are managed in a primary care setting. However, primary healthcare professionals face the challenge of the growing plethora of available treatment options for managing hyperglycaemia, leading to difficultly in making treatment decisions and contributing to treatment and therapeutic inertia. This position statement offers a simple and patient-centred clinical decision-making model with practical treatment recommendations that can be widely implemented by primary care clinicians worldwide through shared-decision conversations with their patients. It highlights the importance of managing cardiovascular disease and elevated cardiovascular risk in people with type 2 diabetes and aims to provide innovative risk stratification and treatment strategies that connect patients with the most effective care.

A disease state approach to the pharmacological management of Type 2 diabetes in primary care: A position statement by Primary Care Diabetes Europe.

Type 2 diabetes and its associated comorbidities are growing more prevalent, and the complexity of optimising glycaemic control is increasing, especially on the frontlines of patient care. In many countries, most patients with type 2 diabetes are managed in a primary care setting. However, primary healthcare professionals face the challenge of the growing plethora of available treatment options for managing hyperglycaemia, leading to difficultly in making treatment decisions and contributing to therapeutic inertia. This position statement offers a simple and patient-centred clinical decision-making model with practical treatment recommendations that can be widely implemented by primary care clinicians worldwide through shared-decision conversations with their patients. It highlights the importance of managing cardiovascular disease and elevated cardiovascular risk in people with type 2 diabetes and aims to provide innovative risk stratification and treatment strategies that connect patients with the most effective care.

Impact on guidelines: The general practitioner point of view.

Primary care physicians are uniquely placed to offer holistic, patient-centred care to patients with T2DM. While the recent FDA-mandated cardiovascular outcome trials offer a wealth of data to inform treatment discussions, they have also contributed to increasing complexity in treatment decisions, and in the guidelines that seek to assist in making these decisions. To assist physicians in avoiding treatment inertia, Primary Care Diabetes Europe has formulated a position statement that summarises our current understanding of the available T2DM treatment options in various patient populations. New data from recent outcomes trials is contextualised and summarised for the primary care physician. This consensus paper also proposes a unique and simple tool to stratify patients into 'very high' and 'high' cardiovascular risk categories and outlines treatment recommendations for patients with atherosclerotic cardiovascular disease, heart failure and chronic kidney disease. Special consideration is given to elderly/frail patients and those with obesity. A visual patient assessment tool is provided, and a comprehensive set of prescribing tips is presented for all available classes of glucose-lowering therapies. This position statement will complement the already available, often specialist-focused, T2DM treatment guidelines and provide greater direction in how the wealth of outcome trial data can be applied to everyday practice.

Safety and efficacy of insulin degludec/liraglutide (IDegLira) added to sulphonylurea alone or to sulphonylurea and metformin in insulin-naïve people with Type 2 diabetes: the DUAL IV trial.

AIM: To investigate the safety and efficacy of insulin degludec/liraglutide (IDegLira), a novel combination product, as add-on therapy for people with Type 2 diabetes uncontrolled on sulphonylurea therapy. METHODS: In this 26-week, double-blind trial, adults with Type 2 diabetes [HbA1c 53-75 mmol/mol (7.0-9.0%)] were randomized to IDegLira (n = 289) or placebo (n = 146) as add-on to pre-trial sulphonylurea ± metformin, titrating to a fasting glycaemic target of 4.0-6.0 mmol/l. Treatment initiation was at 10 dose steps, and maximum dose was 50 dose steps (50 units insulin degludec/1.8 mg liraglutide). RESULTS: The mean HbA1c decreased from 63 mmol/mol (7.9%) to 46 mmol/mol (6.4%) with IDegLira and to 57 mmol/mol (7.4%) with placebo [estimated treatment difference -11 mmol/mol (95% CI -13; -10) or -1.02% (95% CI -1.18; -0.87); P < 0.001]. The HbA1c target of 53 mmol/mol (<7%) was achieved by 79.2% of participants in the IDegLira group vs 28.8% in the placebo group [estimated odds ratio 11.95 (95% CI 7.22; 19.77); P < 0.001]. Mean weight change was +0.5 kg with IDegLira vs -1.0 kg with placebo [estimated treatment difference 1.48 kg (95% CI 0.90; 2.06); P < 0.001]. Confirmed hypoglycaemia occurred in 41.7 and 17.1% of IDegLira- and placebo-treated participants, respectively, with rates of 3.5 vs 1.4 events/patient-years of exposure [estimated rate ratio 3.74 (95% CI 2.28; 6.13); P < 0.001]. IDegLira was generally well tolerated. The rates of serious adverse events were 20.3 and 8.0 per 100 patient-years of exposure with IDegLira and placebo, respectively, without obvious patterns in the type of events. CONCLUSIONS: IDegLira can be used in people uncontrolled with sulphonylurea ± metformin to improve efficacy with a safety profile in line with previous DUAL trials.

A comparison of the assessment and management of cardiometabolic risk in patients with and without type 2 diabetes mellitus in Canadian primary care.

AIM: To investigate the cardiometabolic risk (CMR) assessment and management patterns for individuals with and without type 2 diabetes mellitus (T2DM) in Canadian primary care practices. METHODS: Between April 2011 and March 2012, physicians from 9 primary care teams and 88 traditional non-team practices completed a practice assessment on the management of 2461 patients >40 years old with no clinical evidence of cardiovascular disease and diagnosed with at least one of the following risk factor-T2DM, dyslipidaemia or hypertension. RESULTS: There were 1304 individuals with T2DM and 1157 without. Pharmacotherapy to manage hyperglycaemia, dyslipidaemia and hypertension was widely prescribed. Fifty-eight percent of individuals with T2DM had a glycated haemoglobin (HbA1c) ≤7.0%. Amongst individuals with dyslipidaemia, median low-density lipoprotein cholesterol (LDL-C) was 1.8 mmol/l for those with T2DM and 2.8 mmol/l for those without. Amongst individuals with hypertension, 30% of those with T2DM achieved the <130/80 mmHg target, whereas 60% of those without met the <140/90 mmHg target. The composite glycaemic, LDL-C and blood pressure (BP) target outcome was achieved by 12% of individuals with T2DM. Only 17% of individuals with T2DM and 11% without were advised to increase their physical activity. Dietary modifications were recommended to 32 and 10% of those with and without T2DM, respectively. CONCLUSIONS: Patients at elevated CMR were suboptimally managed in the primary care practices surveyed. There was low attainment of recommended therapeutic glycaemic, lipid and BP targets. Advice on healthy lifestyle changes was infrequently dispensed, representing a missed opportunity to educate patients on the long-term benefits of lifestyle modification.

Utility of non-high-density lipoprotein cholesterol in assessing incident type 2 diabetes risk.

AIMS: Traditional lipid indices have been associated with type 2 diabetes, but limited data are available regarding non-high-density lipoprotein (non-HDL) cholesterol. In view of recent guidelines for the clinical management of dyslipidemia recommending the monitoring of non-HDL cholesterol as a secondary target after achieving the low-density lipoprotein (LDL) cholesterol goal, we aimed to assess the association of non-HDL cholesterol with incident type 2 diabetes and compare its utility as a risk predictor with traditional lipid variables in Aboriginal Canadians. METHODS: Of 606 diabetes-free participants at baseline, 540 (89.1%) returned for 10-year follow-up assessments. Baseline anthropometry, blood pressure, fasting insulin and serum lipids were measured. Fasting and 2-h postload glucose were obtained at baseline and follow-up to determine the incidence of type 2 diabetes. RESULTS: The cumulative incidence of type 2 diabetes was 17.5%. Higher non-HDL cholesterol, total-to-HDL cholesterol ratio, apolipoprotein B, triglyceride and LDL cholesterol and lower HDL cholesterol concentrations were individually associated with incident type 2 diabetes in univariate analyses (all p < 0.05). Non-HDL cholesterol was a superior determinant of incident diabetes compared with LDL cholesterol (comparing C-statistics of univariate models p = 0.01) or HDL cholesterol (p = 0.004). With multivariate adjustment including waist circumference, non-HDL cholesterol remained associated with incident diabetes [odds ratio (OR) 1.42 (95% confidence interval, CI 1.07-1.88)], while LDL cholesterol and HDL cholesterol became non-significant. CONCLUSIONS: Non-HDL cholesterol was associated with incident type 2 diabetes and was superior to LDL cholesterol as a risk predictor in this population. Further studies are required to establish the utility of non-HDL cholesterol in non-Aboriginal populations.

Increased rates of adverse outcomes for gestational diabetes and pre-pregnancy diabetes in on-reserve First Nations Women in Ontario, Canada.

AIMS: To compare the prevalence of diabetes in pregnancy, pregnancy care and adverse pregnancy outcomes in on-reserve First Nations women vs. non-First Nations women in Ontario, Canada. METHODS: A retrospective population-based cohort study was performed. All 487368 live singleton hospital deliveries between 1 April 2002 and 31 March 2010 were identified. Outcomes were defined by linking mothers and infants to provincial healthcare administrative databases. RESULTS: Diabetes in pregnancy was more prevalent in First Nations women (10.3 vs. 6.0%). They received less pregnancy care and had higher rates of adverse outcomes than non-First Nations women with diabetes. CONCLUSIONS: First Nations women are at a higher risk of diabetes in pregnancy and adverse outcomes. This highlights the need for increased care for pregnant First Nations women.

Discordant effects on central obesity, hepatic insulin resistance, and alanine aminotransferase of low-dose metformin and thiazolidinedione combination therapy in patients with impaired glucose tolerance.

Alanine aminotransferase (ALT) predicts incident type 2 diabetes (T2DM), possibly reflecting early fatty liver and hepatic insulin resistance. Thiazolidinediones and metformin can improve fatty liver and hepatic insulin resistance, respectively. In the Canadian Normoglycemia Outcome Evaluation trial, rosiglitazone/metformin (Rosi/Met, 4/1000 mg) reduced incident T2DM by 66% in subjects with impaired glucose tolerance. For insight on the hepatic effects of this therapy in relation to T2DM, we evaluated the temporal changes in waist, hepatic insulin sensitivity (1/Homeostasis Model Assessment of Insulin Resistance) and ALT in the Rosi/Met (n = 103) and placebo (n = 104) arms over median of 3.9 years. Waist did not differ between the arms. Hepatic insulin sensitivity improved in the Rosi/Met arm in year 1, but deteriorated thereafter as in the placebo arm. In contrast, Rosi/Met lowered ALT in year 1 and maintained this effect throughout the trial. Thus, low-dose Rosi/Met had no effect on central obesity, a transient effect on hepatic insulin sensitivity, and a sustained effect on ALT.

Process evaluation of a multi-institutional community-based program for diabetes prevention among First Nations.

Epidemic rates of diabetes among Native North Americans demand novel solutions. Zhiiwaapenewin Akino'maagewin: Teaching to Prevent Diabetes was a community-based diabetes prevention program based in schools, food stores and health offices in seven First Nations in northwestern Ontario, Canada. Program interventions in these three institutions included implementation of Grades 3 and 4 healthy lifestyles curricula; stocking and labeling of healthier foods and healthy recipes cooking demonstrations and taste tests; and mass media efforts and community events held by health agencies. Qualitative and quantitative process data collected through surveys, logs and interviews assessed fidelity, dose, reach and context of the intervention to evaluate implementation and explain impact findings. School curricula implementation had moderate fidelity with 63% delivered as planned. Store activities had moderate fidelity: availability of all promoted foods was 70%, and appropriate shelf labels were posted 60% of the time. Cooking demonstrations were performed with 71% fidelity and high dose. A total of 156 posters were placed in community locations; radio, cable TV and newsletters were utilized. Interviews revealed that the program was culturally acceptable and relevant, and suggestions for improvement were made. These findings will be used to plan an expanded trial in several Native North American communities.

Elevated C-reactive protein in Native Canadian children: an ominous early complication of childhood obesity.

AIM: Subclinical inflammation has been proposed as a pathophysiologic mechanism linking obesity with vascular and metabolic disease. Native North American populations are experiencing high prevalence rates of both (i) childhood obesity and (ii) adult cardiovascular disease (CVD) and type 2 diabetes. Thus, we sought to determine whether subclinical inflammation is an early complication of obesity in Native children. METHODS: Serum concentrations of the inflammatory biomarker C-reactive protein (CRP) were assessed in a population-based, cross-sectional study of the Sandy Lake Oji-Cree community of Northern Ontario, Canada, involving 228 children aged 10-19 years (mean age 14.8). RESULTS: Median CRP in this population was 0.5 mg/l (interquartile range 0.18-1.79 mg/l). CRP levels were higher than age-matched reference data from the Third National Health and Nutrition Examination Survey (NHANES III). Importantly, fully 15.8% of the children of this community had CRP concentrations between 3 and 10 mg/l, a range that identifies adults at high risk of CVD. Moreover, increasing CRP concentration in this paediatric population was associated with an enhanced CV risk profile, consisting of increased adiposity, higher insulin resistance, worsening lipid profile (higher total cholesterol, triglycerides, low-density lipoprotein cholesterol, apolipoprotein B and total cholesterol : high-density-lipoprotein cholesterol ratio), increased leptin and decreased adiponectin. On multivariate analysis, waist circumference and interleukin-6 (IL-6) emerged as independent determinants of CRP concentration. CONCLUSION: Subclinical inflammation is an early complication of childhood obesity in Native children and may foreshadow an increased burden of CVD and type 2 diabetes in the future.

Preventing type 2 diabetes using combination therapy: design and methods of the CAnadian Normoglycaemia Outcomes Evaluation (CANOE) trial.

Several studies have demonstrated that type 2 diabetes mellitus (DM) can be prevented/delayed in subjects with impaired glucose tolerance (IGT) by using pharmacologic agents and/or lifestyle interventions. However, a number of challenges remain, including the translation of lifestyle programmes to the general population and the need to achieve greater risk reductions by using pharmacologic approaches. IGT, like DM, is characterized by insulin resistance, beta-cell dysfunction and increased hepatic glucose production. We believe that the use of combination diabetes therapy would be a particularly effective diabetes prevention strategy. In this context, we initiated the Canadian Normoglycemia Outcomes Evaluation (CANOE) study, a moderately sized, randomized, double-blind, controlled trial. The primary objective of CANOE is to determine whether treatment with metformin plus rosiglitazone, in addition to a healthy living lifestyle programme, will prevent the development of DM. The secondary objective of CANOE is to determine whether this treatment approach will improve cardiovascular risk factors associated with IGT. A total of 200 patients will be recruited in Toronto and London, Ontario, and followed for an average of 4 years (range 3-5 years). Active treatment with metformin (500 mg) plus rosiglitazone (2 mg), administered as one capsule twice daily, will be compared to matched placebo. Subjects will be eligible for randomization if they have IGT and are between the ages of 30-75 years. The primary outcome will be the development of new-onset DM, diagnosed by either two fasting plasma glucose values of >or=7 mmol/l or one positive oral glucose tolerance test with a 2-h plasma glucose value of >11.0 mmol/l during the active drug phase of the trial. With a sample size of 100 participants per group, we will be able to detect a relative risk reduction of 45%, with a two-sided log-rank test with a significance level of 0.05 and 80% power, assuming that the median time to progression is 8 years in the control group and that participants will be recruited over 2 years and followed for an average of 4 years. In conclusion, the CANOE study will determine whether combination pharmacological therapy combined with a lifestyle intervention programme can significantly modify the development of diabetes in high-risk Canadians.

The results of immediate re-repair of zone 1 and 2 primary flexor tendon repairs which rupture.

This study reports the outcome of immediate re-repair of primary flexor tendon repairs in zones 1 and 2 of the fingers which had ruptured. Between June 1989 and May 2003, a total of 62 fingers in 61 patients presented with ruptured flexor tendon repairs within 48 hours from rupture. Immediate re-repair and rehabilitation was carried out in 44 fingers (71%) in 43 (70%) patients. Thirty-six patients completed the 8-week therapy programme after re-repair in 37 fingers. Nine (24%) had excellent, 10 (27%) good, 5 (14%) fair and 13 (35%) had poor results when assessed by the original Strickland method. Five fingers in five patients ruptured the re-repair. Poor results and second ruptures were particularly common after re-repair of ruptured tendon repairs in the little finger. In the light of these findings, a policy for dealing with ruptured primary flexor tendon repairs in the fingers is suggested.

A randomized trial of adding insulin glargine vs. avoidance of insulin in people with Type 2 diabetes on either no oral glucose-lowering agents or submaximal doses of metformin and/or sulphonylureas. The Canadian INSIGHT (Implementing New Strategies with Insulin Glargine for Hyperglycaemia Treatment) Study.

AIMS: Insulin is generally withheld until people with Type 2 diabetes are unresponsive to other therapies. However, its potential advantages suggest that it could be added earlier to achieve glycaemic goals; this possibility was tested in a clinical trial. METHODS: Consenting adults aged 18-80 years with Type 2 diabetes for at least 6 months, HbA1c of 7.5-11%, and on 0, 1 or 2 oral agents, were randomized to one of two therapeutic approaches for 24 weeks: evening insulin glargine plus self-titration by 1 unit/day if the fasting plasma glucose (FPG) was > 5.5 mmol/l; or conventional therapy with physician adjustment of oral glucose-lowering agents if capillary FPG levels were > 5.5 mmol/l. The primary outcome was the first achievement of two consecutive HbA1c levels

Development of an integrated diabetes prevention program with First Nations in Canada.

Type 2 diabetes mellitus is a major cause of morbidity and mortality among First Nations in Canada. We used multiple research methods to develop an integrated multi-institutional diabetes prevention program based on the successful Sandy Lake Health and Diabetes Project and Apache Healthy Stores programs. In-depth interviews, a structured survey, demonstration and feedback sessions, group activities, and meetings with key stakeholders were used to generate knowledge about the needs and resources for each community, and to obtain feedback on SLHDP interventions. First Nations communities were eager to address the increasing epidemic of diabetes. Educating children through a school prevention program was the most popular proposed intervention. Remote communities had poorer access to healthy foods and more on-reserve media and services than the smaller semi-remote reserves. While the reserves shared similar risk factors for diabetes, variations in health beliefs and attitudes and environmental conditions required tailoring of programs to each reserve. In addition, it was necessary to balance community input with proven health promotion strategies. This study demonstrates the importance of formative research in developing integrated health promotion programs for multiple communities based on previously evaluated studies.

Clinical and genetic associations with hypertriglyceridemic waist in a Canadian aboriginal population.

OBJECTIVES: To determine the prevalence of 'hypertriglyceridemic waist' (HTGW) in Oji-Cree, to examine its interaction with hepatic nuclear factor-1alpha (HNF1A) in association with type 2 diabetes, and to characterize its putative genetic determinants. METHOD: The presence or absence of HTGW was determined in 522 Oji-Cree subjects (223 males, 299 females), >or=18 years of age, in whom physical measurements and fasting plasma analyte concentrations were gathered, and a 75-g oral glucose tolerance test was administered, as part of a cross-sectional study. Subjects were genotyped for HNF1A codon 319, angiotensinogen (AGT) codons 174 and 235, G-protein beta3-subunit (GNB3) nucleotide 825, fatty acid-binding protein (FABP2) codon 54, nucleotides -455 and -482 of the apolipoprotein (apo) C-III (APOC3) promoter, and a 5-bp insertion/deletion polymorphism within the 3'-untranslated region of protein phosphatase 1 regulatory subunit 3 (PPP1R3). RESULTS: The unadjusted prevalence of HTGW in Oji-Cree adults was 20.5%, with more males affected than females (27.8 vs 15.1%, P=0.0004). Logistic regression analysis, adjusted for age and gender, showed type 2 diabetes was associated with both HNF1A G319S (odds ratio (OR) 4.85, 95% CI 2.45, 9.58) and HTGW (OR 4.96, 95% CI 2.49, 9.88). When the HNF1A mutation and HTGW were present in combination, the OR for type 2 diabetes was markedly increased (OR 43.2, 95% CI 12.4, 150). In women only, both GNB3 825C>T and FABP2 A54T genotypes were significantly associated with HTGW (OR 2.02, 95% CI 1.01, 4.05 and OR 1.95, 95% CI 1.01, 3.74, respectively). CONCLUSIONS: HTGW is prevalent in Oji-Cree, especially in men. The ORs for type 2 diabetes were similar ( approximately 5-fold) for subjects with either the presence of HTGW or the private HNF1A G319S mutation. These two independent risk factors acted synergistically to confer an even greater increased risk of type 2 diabetes.

Characteristics and prevalence of the metabolic syndrome among three ethnic groups in Canada.

OBJECTIVE: To compare the characteristics and prevalence of the metabolic syndrome (MetS) among Native Indians, Inuit, and non-Aboriginal Canadians. METHODS: The study was based on four cross-sectional studies conducted in the late 1980s and early 1990s involving three ethnic groups living in contiguous regions in central Canada: Oji-Cree Indians from several reserves in northern Ontario and Manitoba, Inuit from the Keewatin region of the Northwest Territories, and non-Aboriginal Canadians (predominantly of European heritage) in the province of Manitoba. The MetS was identified among adult subjects according to the National Cholesterol Education Program (NCEP) definition. Prevalence rates were standardized to the 1991 Canadian national population. RESULTS: The age-standardized prevalence of the MetS varied by ethnic group, ranging from as high as 45% among Native Indian women to as low as 8% among Inuit men. Compared with Canadians of European origin, Indians had a worse metabolic profile, while Inuit had a better metabolic profile except for a high rate of abdominal obesity. The NCEP criteria in identifying individuals with the MetS were compared to those of the World Health Organization (WHO) in a subset of subjects with the requisite laboratory data. There was moderate agreement between the NCEP and WHO definitions, with a kappa value of 0.63 (95% confidence interval 0.56-0.70). CONCLUSIONS: The results indicate that the MetS is prevalent in diverse ethnic groups in Canada but varies in the pattern of phenotypic expression. Given the diverse nature of these populations, careful consideration should be given to developing culturally appropriate community-based prevention strategies aimed at reducing the frequency of this syndrome.

The significance of extensor tendon tethering and dorsal joint capsule tightening after injury to the hand.

This paper examines the clinical problem of extensor tendon tethering and/or dorsal joint capsule tightening secondary to hand injury. One hundred and forty-one patients were examined 13 to 51 months after hand injuries of varying severity. Fifty-six patients (40%) had suffered simple and eighty-five patients (60%) complex injuries. Seventy-four (52%) of the 141 patients had no extensor tendon tethering and/or dorsal joint capsule tightening. In 30 (21%), the extensor tendon tethering and/or dorsal joint capsule tightening was considered to be "obvious" in that it was easily seen on examination using various commonly used clinical tests of finger flexion and extension. In 37 (26%), the extensor tendon tethering and/or dorsal joint capsule tightening was considered to be of "lesser degree" because it was only evident on application of specific tests which are described in this paper. Of the 37, 21 (56%) described themselves as being unable to make a "proper" fist with the injured hand, 33 (89%) had pain or discomfort on the dorsum of the injured hand and/or fingers on gripping (P < 0.01) and 25 (70%) had weakness of power of gripping (P < 0.01). Thirty-two (87%) complained of functional problems at work, with activities of daily living or with the pursuit of their hobbies.

Synergism between mutant HNF1A and the metabolic syndrome in Oji-Cree Type 2 diabetes.

AIMS: To determine the prevalence of the metabolic syndrome in the Sandy Lake Oji-Cree and to examine its interaction with HNF1A in association with impaired glucose tolerance and Type 2 diabetes. METHODS: Using data collected from the Sandy Lake Health and Diabetes Project (1993-1995), the presence or absence of the metabolic syndrome was determined in 515 Oji-Cree subjects, > or = 18 years of age. In the original study, fasting plasma analytes were measured, a 75-g oral glucose tolerance test was administered, and subjects were genotyped for HNF1A G319S. RESULTS: The unadjusted prevalence of the metabolic syndrome in the Oji-Cree adults was 29.9%. The adjusted odds ratio (OR) and 95% confidence interval for Type 2 diabetes among subjects who carried the HNF1A G319S mutation and had the modified metabolic syndrome (excluding hyperglycaemia) was 20.3 (6.94, 59.6). Adjusted ORs for Type 2 diabetes for subjects with either the HNF1A G319S mutation alone or the modified metabolic syndrome alone were 5.56 (2.85, 10.9) and 4.84 (2.53, 9.27), respectively. The risk of having impaired glucose tolerance was not influenced by the presence of either factor. CONCLUSIONS: The risk of Type 2 diabetes was similar (approximately five-fold increased) for subjects with either the presence of the modified metabolic syndrome or the private HNF1A G319S mutation. Interestingly, when present in combination, the two independent risk factors appeared to act synergistically to confer an even greater increased risk of Type 2 diabetes.