Sara Meltzer

Following in mother's footsteps? Mother-daughter risks for insulin resistance and cardiovascular disease 15 years after gestational diabetes.

Diabet. Med. 27, 257–265 (2010)

Oxysterol as a Marker of Atherogenic Dyslipidemia in Adolescence

CONTEXT Oxysterols represent potentially important oxidative stress biomarkers in adolescence. OBJECTIVE The objective of the study was to examine the relationship between the concentrations of serum enzymatically and nonenzymatically generated oxysterols, measures of obesity, and metabolic components including insulin resistance and levels of blood pressure and serum lipids. DESIGN This was a cross-sectional study. SETTING All subjects were examined between 2003 and 2005 at a hospital, a part of a follow-up evaluation mother-daughter pairs representing pregnancies affected or unaffected by gestational diabetes that resulted in the deliveries in 1989-1991. SUBJECTS Subjects included a subset (n=89) of the total study population of 189 adolescent girls with a mean age of 15.32+/-0.65 yr and body mass index of 22.54+/-3.98 kg/m2. MAIN OUTCOME MEASURES Measures included serum levels of the oxysterols 7alpha-hydroxy-cholesterol, 7beta-hydroxycholesterol, and 7-ketocholesterol; and body mass index, homeostasis model assessment insulin resistance index, fasting insulin, fasting glucose, blood pressure, total cholesterol, non-high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and apolipoprotein B (ApoB). RESULTS Serum oxysterol concentrations in the adolescent cohort correlated positively with insulin (P<0.05), total cholesterol (P<0.05), non-high-density lipoprotein cholesterol (P<0.05), low-density lipoprotein cholesterol (P<0.05), and ApoB (P<0.01). ApoB and fasting insulin were found to be the major determinants of serum oxysterols after adjustment for body mass index. Being a daughter of gestational diabetes pregnancy alone did not seem to be a predisposing factor to increased oxidative stress in our cohort. CONCLUSION Serum oxysterol concentrations increase with obesity, insulin, and ApoB, which are established derangements associated with the metabolic syndrome.

The association of desaturase 9 and plasma fatty acid composition with insulin resistance-associated factors in female adolescents.

Desaturase 9 (Delta 9), which converts saturated fatty acids (SFAs) into monounsaturated fatty acids, is an important component in leptin-mediated energy homeostasis in rodent models. Few human studies, however, have been performed regarding the clinical relevance of Delta 9, particularly whether Delta 9 is involved in the relationship between blood fatty acid profiles and insulin resistance-associated factors. The aim of the present study was to examine fatty acid data from 178 apparently healthy female adolescents and determine whether (a) Delta 9 has independent associations with adiposity, insulin resistance level, and fasting plasma polyunsaturated fatty acids (PUFAs); (b) Delta 9 is a predictor of fasting blood lipid profile; and (c) the associations between fasting plasma fatty acid component and insulin resistance level are independent of abdominal obesity level. Desaturase 9-16 (surrogate of Delta 9 as calculated by plasma ratio C16:1 n-7/C16:0) correlated with waist girth (r = .160, P < .05), homeostasis model assessment of insulin resistance (HOMA-IR) (r = .201, P < .01), plasma PUFAs (eg, C20:4 n-6 [r = -.269, P < .001], C22:6 n-3 [r = -.274, P < .001]). After adjustment for dietary SFAs, Delta 9-16 had stronger correlation with waist (r = .227, P < .01) and significant correlation with PUFAs, whereas it had a nonsignificant correlation with HOMA-IR. The same pattern was observed with Delta 9-18 (surrogate of Delta 9 as calculated by plasma ratio C18:1 n-9/C18:0). After adjustment for dietary SFAs, waist, and HOMA-IR, Delta 9-16 and Delta 9-18 were still positive predictors of triglyceride (both P < .001) and apolipoprotein B (Delta 9-18, P < .001; Delta 9-16, P = .052). After adjustment for waist, HOMA-IR only remained a positive determinant of medium-chain SFAs (C14:0, P < .001; C16:0, P < .05); but it emerged to be inversely related to C20:4 n-6 (P < 0.1). The positive and independent associations of medium-chain SFAs with insulin resistance level suggest their vital roles in diabetes pathogenesis, whereas certain PUFAs such as C20:4 n-6 appear to be protective. The observed associations of Delta 9 with adiposity and plasma lipid profile in these apparently healthy female adolescents support the concept derived from rodent models that Delta 9 activity is independently reflective of higher body mass index and higher circulatory triglyceride levels.

Strategies for implementing the WHO diagnostic criteria and classification of hyperglycaemia first detected in pregnancy

The World Health Organization (WHO) has recently released updated recommendations on Diagnostic Criteria and Classification of Hyperglycaemia First Detected in Pregnancy which are likely to increase the prevalence of gestational diabetes mellitus (GDM). Any increase in the number of women with GDM has implications for health services since these women will require treatment and regular surveillance during the pregnancy. Some health services throughout the world may have difficulty meeting these demands since country resources for addressing the diabetes burden are finite and resource allocation must be prioritised by balancing the need to improve care of people with diabetes and finding those with undiagnosed diabetes, including GDM. Consequently each health service will need to assess their burden of hyperglycaemia in pregnancy and decide if and how it will implement programmes to test for and treat such women. This paper discusses some considerations and options to assist countries, health services and health professionals in these deliberations.

Strategies to optimize participation in diabetes prevention programs following gestational diabetes: a focus group study.

Objective We performed a qualitative study among women within 5 years of Gestational Diabetes (GDM) diagnosis. Our aim was to identify the key elements that would enhance participation in a type 2 diabetes (DM2) prevention program. Research Design and Methods Potential participants received up to three invitation letters from their GDM physician. Four focus groups were held. Discussants were invited to comment on potential facilitators/barriers to participation and were probed on attitudes towards meal replacement and Internet/social media tools. Recurring themes were identified through qualitative content analysis of discussion transcripts. Results Among the 1,201 contacted and 79 eligible/interested, 29 women attended a focus group discussion. More than half of discussants were overweight/obese, and less than half were physically active. For DM2 prevention, a strong need for social support to achieve changes in dietary and physical activity habits was expressed. In this regard, face-to-face interactions with peers and professionals were preferred, with adjunctive roles for Internet/social media. Further, direct participation of partners/spouses in a DM2 prevention program was viewed as important to enhance support for behavioural change at home. Discussants highlighted work and child-related responsibilities as potential barriers to participation, and emphasized the importance of childcare support to allow attendance. Meal replacements were viewed with little interest, with concerns that their use would provide a poor example of eating behaviour to children. Conclusions Among women within 5 years of a GDM diagnosis who participated in a focus group discussion, participation in a DM2 prevention program would be enhanced by face-to-face interactions with professionals and peers, provision of childcare support, and inclusion of spouses/partners.

Effects of a Diet Higher in Carbohydrate/ Lower in Fat Versus Lower in Carbohydrate/Higher in Monounsaturated Fat on Postmeal Triglyceride Concentrations and Other Cardiovascular Risk Factors in Type 1 Diabetes

OBJECTIVE To compare the effects of a eucaloric diet higher in carbohydrate/lower in fat versus lower in carbohydrate/higher in monounsaturated fat on postmeal triglyceride (TG) concentrations and other cardiovascular disease risk factors in nonobese subjects with type 1 diabetes and in good glycemic control. RESEARCH DESIGN AND METHODS In a parallel group design study, 30 subjects were randomly assigned and completed one of the two eucaloric diets. Assessments included: BMI, blood pressure, A1C, plasma lipids, and markers of oxidation, thrombosis, and inflammation. At 6 months, subjects were hospitalized for 24 h to measure plasma TG excursions. RESULTS There were no significant differences between groups other than decreased plasminogen activator inhibitor 1 (PAI-1) levels and weight gain in the lower-carbohydrate/higher–monounsaturated fat group. During the 24-h testing, the lower-carbohydrate/higher–monounsaturated fat group had a lower plasma TG profile. CONCLUSIONS A diet lower in carbohydrate/higher in monounsaturated fat could offer an appropriate choice for nonobese type 1 diabetic individuals with good metabolic and weight control.

Optimizing insulin delivery: assessment of three strategies in intensive diabetes management

SUMMARY

Plasma Fatty Acids and Desaturase Activity Are Associated with Circulating Adiponectin in Healthy Adolescent Girls

CONTEXT Adiponectin can be a potential predictor of future metabolic derangements and some preliminary evidence supports the role of dietary fat in influencing adiponectin levels thus, the dietary determinants of adiponectin were investigated. OBJECTIVE The objective of the study was to evaluate the association of adiponectin concentrations with plasma fatty acids and indices of endogenous fatty acid metabolism. DESIGN This was a cross-sectional descriptive analysis to investigative the determinants of adiponectin. SETTING All subjects were examined at a large tertiary care center located in Montréal (Québec, Canada) between 2004 and 2006. SUBJECTS Subjects included 180 postpubertal, adolescent daughters (age range 13.6-17.3 yr) from a 15-yr retrospective cohort of mother-daughter pairs representing gestational diabetes mellitus affected (cases) and nonaffected (controls) pregnancies between 1989 and 1991. MAIN OUTCOME MEASURES Plasma adiponectin concentrations, plasma fatty acids presented grouped by series name and as individual fatty acids (reported as percent of total), and calculated indices of fatty acid metabolism were measured. RESULTS In linear regression analyses, adjusting for both waist circumference and insulin measured 2 h after the onset of an oral glucose tolerance test, the docosahexaenoic acid sufficiency index (an indicator of docosahexaenoic acid status) and alpha-linolenic acid (C18:3 n-3) were significantly negatively associated (P <or= 0.05) with adiponectin. After accounting for dietary fat intake, these associations disappeared, indicating an effect of diet. However, the long-chain saturated fatty acid, lignoceric (C24:0), was positively associated (P <or= 0.05) and Delta 9-18 desaturase activity (estimated from the ratio of 18:1 n-9/18:0) was significantly inversely (P <or= 0.01) associated with adiponectin concentrations. CONCLUSIONS Adiponectin, an inverse marker of metabolic derangements, was associated with desaturase activity, indicating that possible functional alterations in fatty acid metabolism may already be present in young healthy adolescent females.

Conjoint Associations of Gestational Diabetes and Hypertension With Diabetes, Hypertension, and Cardiovascular Disease in Parents: A Retrospective Cohort Study

Abstract The conjoint association of gestational diabetes mellitus (GDM) and gestational hypertension (GH) with cardiometabolic disease has not been well studied. We evaluated a combined GDM/GH risk indicator in both mothers and fathers because of shared spousal behaviors and environments. In the present population-based retrospective cohort study, GH was identified in matched pairs of mothers with GDM or without GDM (matched on age group, health region, and year of delivery) who had singleton live births in Quebec, Canada (1990–2007). A total of 64,232 couples were categorized based on GDM/GH status (neither, either, or both). Associations with diabetes, hypertension, and a composite of cardiovascular disease (CVD) and mortality were evaluated using Cox proportional hazard models (from 12 weeks postpartum to March 2012). Compared with having neither GDM nor GH, having either was associated with incident diabetes (hazard ratio (HR) = 14.7, 95% confidence interval (CI): 12.9, 16.6), hypertension (HR = 1.9, 95% CI: 1.8, 2.0), and CVD/mortality (HR = 1.4, 95% CI: 1.2, 1.7). We found associations of greater magnitude among participants who had both (for diabetes, HR = 36.9, 95% CI: 26.0, 52.3; for hypertension, HR = 5.7, 95% CI: 4.9, 6.7; and for CVD/mortality, HR = 2.4, 95% CI: 1.6, 3.5). Associations with diabetes were also observed in fathers (for either, HR = 1.2, 95% CI: 1.1, 1.3; for both, HR = 1.8, 95% CI: 1.4, 2.3). In conclusion, we found associations of a combined GDM/GH indicator with cardiometabolic disease in mothers and with diabetes in fathers, with stronger associations when both GDM and GH were present.

Prepregnancy care: a shared responsibility.

The effective management of pregnancies complicated by diabetes is a shared responsibility—an equal partnership between health care professionals and a responsible woman. Over the last 30 years, major advances in our understanding of the pathophysiology and care of diabetes has led to the hope that pregnancy outcomes for women with diabetes would be similar to the outcomes for women without diabetes as stated in the goal of the Saint Vincents Declaration in 1989 (1). Unfortunately this has not been realized with the risk of congenital malformations, stillbirths, and neonatal death remaining as high as 3–10 times that of the background population (2–5). For over a decade, major evidence-based guidelines have called for the counseling of women of child-bearing age with diabetes about the need for family planning and excellent control prior to conception (6–9). Also, preconception care provides the opportunity for the woman and her health caregivers to evaluate nutritional needs, the presence and extent of any micro-/macrovascular complications, and to adjust medications or diabetes management plans before pregnancy occurs. Ideally, every woman with known diabetes would not only have prepregnancy counseling but actually receive effective prepregnancy care. This has been an elusive goal that is underlined in the article by Murphy et al. (10) in this issue of Diabetes Care . These investigators developed a remarkable “marketing” plan, which included a website, lively and encouraging pamphlets mailed directly to potential patients, as well as local and community educational activities for health professionals. Disappointingly, only 27% of the eligible women with pregestational diabetes actually presented for prepregnancy care. This mirrors similar attempts in Maine (34%) using a statewide community–based educational program for health providers and Ohio (37% in the third 5-year phase of a 15-year program) to optimize access and use of prepregnancy counseling and …