Relationships of vitamin D status and markers of skeletal health to metabolic syndrome and markers of glucose homeostasis among inuit adults: the international polar year inuit health survey 2007-2008

In Canada, Inuit are facing a rapid nutrition transition away from consumption of traditional food (TF) which coincides with a higher prevalence of obesity, type 2 diabetes mellitus (DM2) and lower vitamin D status.Vitamin D status is inversely associated with the risks of developing prediabetes, metabolic syndrome (METS) and DM2.Cross talk between energy metabolism and bone through osteocalcin is implicated in the pathophysiology and etiology of DM2.Epidemiological studies show that osteocalcin associates with reduced insulin resistance and enhanced pancreatic secretion of insulin.This thesis consists of 4 studies using data from Inuit adults (≥18 y) who participated in the cross-sectional 2007-2008 International Polar Year Inuit Health Survey conducted in three arctic regions, Nunavut, Nunatsiavut and Inuvialuit Settlement Region.Measurements included fasting plasma glucose (FPG), serum 25-hydroxyvitamin D (25(OH)D), insulin, serum lipids, blood pressure, leptin, adiponectin, osteocalcin, red blood cell fatty acids (RBC FA) and forearm bone mineral density (FaBMD).Dietary data were obtained from a 24-h dietary recall and a food frequency questionnaire (FFQ).Study 1: The primary aim (n=1418) of this study was to examine whether vitamin D status among Inuit adults is associated with fasting plasma glucose (FPG) and homeostatic model assessment of insulin resistance (HOMA-IR) after adjustment for covariates.A secondary aim (n=1250) was to explore if adipokines further explained FPG and HOMA-IR.Serum 25(OH)D (per 30 nmol/L) was associated with a lower HOMA-IR (β= -0.058; 95% CI: -0.111 to -0.005, P< 0.05), but not FPG (β= -0.031; 95% CI: -0.14 to 0.080, P> 0.05) after adjustment for age, sex, arctic region, body mass index (BMI) and variables representing TF intakes and RBC FA.There was a positive association between marine mammal intake and FPG and HOMA-IR.Arctic region modulated both FPG and HOMA-IR.Adiponectin was III inversely related to HOMA-IR, leptin was positively related to both FPG and HOMA-IR, and RBC-Omega 3 was inversely related to FPG. Study 2:The objective was to assess whether increases in 25(OH)D and TF intake were associated with a reduction in METS (n=1725) and its components or DM2 (n=1857) after adjustment for covariates.It was found that greater intake of total TF was not associated with lower odds of METS (OR: 0.88; 95% CI: 0.74 to 1.05, P= 0.158), and the association between serum 25(OH)D and METS was inconclusive (OR: 0.86; 95% CI: 0.71 to 1.03, P= 0.107).Higher serum 25(OH)D lowered the odds of serum high triglyceride (TG) and low serum high density lipoproteins (HDL), whereas higher intakes of fish lowered the odds of a high ratio of serum low density lipoprotein (LDL) to HDL.Being from Nunatsiavut relative to Nunavut and greater marine mammal intake were associated with higher odds for METS.Neither serum 25(OH)D or TF were associated with DM2, but arctic region, obesity and RBC-Sat modulated the odds of DM2.Study 3: The objective was to assess the association between serum osteocalcin and HOMA-IR and FPG (n=256).Although serum osteocalcin was inversely correlated with HOMA-IR (r = -0.17,P= 0.005) and FPG (r = -0.14,P= 0.023), osteocalcin was not associated with HOMA-IR (β= 0.001, 95% CI: -0.023 to 0.025, P= 0.913) or FPG (β= 0.008; 95% CI: -0.146 to 0.162, P= 0.917) in the fully adjusted models. Study 4:The objective was to examine bone health in Inuit women with impaired fasting plasma glucose (IFG) and DM2.FaBMD was not different between cases of DM2 versus control and cases of IFG versus controls, but being free of osteoporosis was more common in cases of DM2 versus controls (OR: 12.8; 95% CI: 1.5 to 109.9, P= 0.016).Fish and marine mammal intakes were positively associated with FaBMD.Conclusions: In summary, in Inuit adults serum 25(OH)D, RBC-Omega3 and fish are protective against insulin resistance and metabolic abnormalities.Serum osteocalcin was not IV related to glucose regulation in this study, whereas DM2 could be associated with higher FaBMD.It appears that metabolic abnormalities in Inuit adults are related to geographical distribution, with people in Nunatsiavut and Inuvialuit Settlement Regions having higher rates of metabolic abnormalities relative to Nunavut.Furthermore, differences were noted regarding how dietary factors modulated diseases, for example serum 25(OH)D was inversely associated with insulin resistance and dyslipidemia, but not IFG and DM2, suggesting that serum 25(OH)D is protective before DM2 is evident.These results indicate that fish is metabolically a more neutral source of nutrients including vitamin D and that traditional lifestyles remain protective against chronic diseases.V RÉSUMÉ Au Canada, les Inuits sont confrontés à une transition nutritionnelle rapide loin de la consommation d'aliments traditionnels (TF) qui coïncide avec une prévalence plus élevée de l'obésité, du diabète de type 2 (DM2) et un statut inférieur de vitamine D. Le statut en vitamine D est inversement associé à des risques de développement du prédiabète, du syndrome métabolique (METS) ainsi que le DM2.La diaphonie entre le métabolisme énergétique et de l'os par l'ostéocalcine est impliquée dans la physiopathologie et l'étiologie de DM2.Les études épidémiologiques démontrent que l'ostéocalcine est associée à une reduction de la résistance à l'insuline ainsi qu'une sécrétion accrue d'insuline du pancréas.Cette thèse est composée de 4 études utilisant des données des adultes inuits (≥18 ans) qui ont participé à l'enquête transversale de 2007-2008: International Polar Year Inuit Health Survey; menée dans trois régions arctiques: Nunavut, Nunatsiavut et région désignée des Inuvialuit.Les mesures comprenaient la glycémie à jeun (FPG), le sérum de 25hydroxyvitamine D (25(OH)D), l'insuline, les lipides sériques, la pression artérielle, la leptine, l'adiponectine, l'ostéocalcine, les acides gras des globules rouges (RBC FA) et la densité minérale des os de l'avant-bras (FaBMD).Les données alimentaires ont été obtenues à partir d'un rappel alimentaire de 24 h et un questionnaire de fréquence alimentaire (FFQ).Étude 1: Le premier objectif (n= 1418) de cette étude était d'examiner si le statut en vitamine D chez les adultes inuits est associée à la glycémie à jeun (FPG) et l'évaluation du modèle homéostatique de résistance à l'insuline (HOMA-IR) après ajustement pour les covariables.Un objectif secondaire (n= 1250) était d'explorer si L'Adipokine outre expliqué FPG et HOMA -IR.Sérum 25(OH)D (par 30 nmol/L) a été associée à une plus faible HOMA-IR (β = -0.058;IC à 95%: -0.111 to -0.005, P< 0.05), mais pas FPG (β =-0.032;IC à 95% :-0.14 à 0.080, P> 0.05) après ajustement pour l'âge, le sexe, la région arctique, l'indice de masse corporelle (IMC) et les variables représentant les apports de TF et RBC FA.Il y X

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