Thatchers Thoughts: Metabolic Issues

Women with diabetes at higher risk of heart disease than men

Title: Impact of diabetes on coronary artery disease in women and men: a meta-analysis of prospective studies
Author: W. L. Lee, et al.
Address: Ontario, Canada 
Source: Diabetes Care 23:962-968 (July) 2000

Summary: While women are at a much lower risk of coronary disease mortality than men, it is commonly believed that women with diabetes lose this advantage. In fact, it is thought that diabetes increases the risk of heart disease in women, putting them at a higher risk than men. All past prospective cohort studies containing both men and women, and both patients with and without diabetes, were examined. After combining studies that adjusted for other cardiac risk factors, the relative risk of coronary death from diabetes was statistically significant at 2.58 for women and 1.85 for men. It was concluded that the impact of diabetes on the risk of coronary death is significantly greater for women than men.

Comment: This remains controversial, but has very important implications for those with PCOS who also have insulin resistance and therefore, a higher risk for developing type 2 diabetes. It is recently reported that a blood lipid profile is a most important and under utilized diagnostic test in women. Abnormal lipid profiles may help predict who is at risk. 

Cost of diabetes starts well before its diagnosis

Title: Type 2 diabetes: Incremental medical care costs during the eight years preceding diagnosis 
Author: G. A. Nichols, et al. 
Address: Portland, Oregon
Source: Diabetes Care 23:1654-1659 (November) 2000

Summary: U sing records from a large group-model HMO, researchers determined the costs of medical care prior to diagnosis for all of the members with type 2 diabetes who were newly diagnosed between 1988 and 1995. Their goal was to analyze the cost of medical care incurred during the eight years preceding the diagnosis of type 2 diabetes. In order to isolate incremental costs (the costs caused by the future diagnosis of diabetes), the authors subtracted the costs of individually age- and sex-matched HMO participants without impending diabetes from the costs of participants who were destined to receive the diagnosis. Additionally, authors compared the prediagnosis medical costs with the medical costs incurred during the first three years after diagnosis. Researchers discovered that an economic burden due to impending diabetes is obvious for a minimum of eight years prior to the actual diagnosis, beginning with outpatient and pharmacy costs. During the eight year period, diabetes associated incremental costs averaged $1205 per patient per year. Costs increased during the final three years prior to diagnosis, averaging $1913 per patient per year. Incremental costs during the year immediately preceding diagnosis were equivalent to those in the second and third post-diagnostic years. Researchers concluded that incremental costs of diabetes begin at least eight years before diagnosis and increase just prior to and immediately following diagnosis. Interestingly, the vast majority of these costs are for conditions normally unrelated to diabetes or its complications.

Comment: We may be seeing the insulin resistant PCO patient 20 years before the diagnosis of diabetes. Can diabetes be prevented?


Birth weight and risk of type 2 diabetes

Title:The fetal and childhood growth of persons who develop type 2 diabetes
Author: T. Forsen, et al.
Address: Helsinki, Finland
Source: Annals of Internal Medicine 133: 176-182 (August) 2000
Summary: Because type 2 diabetes is linked to low birthweight followed by obesity in adulthood, researchers speculated that those who develop the disease might have a particular pattern of growth from birth through childhood. Thus, they examined the relation of type 2 diabetes to size at birth and childhood growth. Researchers identified 471 men and women born in Helsinki between 1924 and 1933, and still lived in Finland in 1971, who developed type 2 diabetes. The cumulative incidence of type 2 diabetes was 7.9% in men and 5.4% in women. The incidence increased with decreasing birthweight, birth length, ponderal index, and placental weight. The odds ratio for type 2 diabetes was 1.38 for each 1 kg decrease in birthweight. The mean weights and heights of the children at 7 years of age who later developed type 2 diabetes were about average. Thereafter, their growth in weight and height was accelerated until 15 years of age. Children of both sexes whose mothers had a high body mass index in pregnancy had more rapid growth during childhood and an increased incidence of type 2 diabetes. Researchers concluded that their findings are consistent with the hypothesis that type 2 diabetes is programmed in utero in association with low rates of fetal growth. 
Comment: The relationship between low birthweight and insulin resistance is clearly established. There has been less information on birthweight and diabetes. There also seems to be an association between low birthweight and premature adrenarche (pubic hair development). One hypothesis is that stress related to growth restriction results in a premature activation of the adrenal axis. This same effect could contribute to the development of PCOS. A potential outcome of the additional possible effect is the development of PCOS, possibly a non-genetic cause of PCOS. To the contrary, large babies are sometimes associated with gestational diabetes, also a known risk factor for later development of type 2 diabetes.

Maternal age and risk of type 1 diabetes

Title: Influence of maternal age at delivery and birth order on risk of type 1 diabetes in childhood: prospective population based family study
Author: P. Bingley, et al. 
Address: Bristol, England
Source:British Medical Journal 321: 420-424 (August) 2000

Summary: In a prospective population based family study, researchers studied the impact of parental age at delivery and birth order on subsequent risk of childhood diabetes. Subjects were 1375 families in which one child or more had diabetes. Of 3221 offspring, 1431 had diabetes and 1790 remained non-diabetic at a median age of 16.1 years. It was discovered that maternal age at delivery was strongly related to the risk of type 1 diabetes in the offspring. The risk increased by 25% for each five year increase of maternal age, so that maternal age at delivery of greater than or equal to 45 years was associated with a relative risk of 3.11 when compared with a maternal age of less than 20 years. Paternal age was also associated with a 9% increase for each five year increase in paternal age. However, the relative risk of diabetes, adjusted for parental age at delivery and sex of offspring, decreased with increasing birth order. The overall effect was a 15% risk reduction per child born. Researchers speculated that the increase in maternal age at delivery in the United Kingdom over the past two decades could partly account for the rise in incidence of childhood diabetes over this period.

Comment: A curious association, but a mechanism is still lacking. 

Hormonal replacement therapy and diabetes

Title: The effect of hormonal replacement therapy on the vascular reactivity and endothelial function of healthy individuals and individuals with type 2 diabetes 
Author: S. Lim, et al
Address: Boston, MA
Source: The Journal of Clinical Endocrinology & Metabolism 84: 4159-4164 (November) 1999

Summary: Researchers studied the effects of HRT on the microvascular reactivity and endothelial function of women with and without diabetes. Participants included 28 healthy premenopausal women, 16 premenopausal women with type 2 diabetes, 12 healthy postmenopausal women, 17 postmenopausal women with diabetes, 13 healthy postmenopausal women on HRT, and 11 postmenopausal women with diabetes on HRT. Laser Doppler flowmetry was used to measure forearm cutaneous vasodilatation in response to iontophoresis of 1% acetylcholine and 1% sodium nitroprusside. The endothelium-dependent vasodilation was significantly higher in premenopausal healthy women compared to premenopausal diabetic women. Endothelium-dependent vasodilation was also higher in postmenopausal healthy women on HRT compared with postmenopausal diabetic women on HRT, postmenopausal healthy women without HRT, and postmenopausal diabetic women without HRT. A similar pattern of responses was observed in the endothelium-independent vasodilation. Soluble intercellular adhesion molecule (sICAM) was also measured among all the women with diabetes. Premenopausal women with diabetes and postmenopausal women with diabetes on HRT had lower sICAM levels compared with the postmenopausal diabetic women without HRT. Researchers concluded that menopausal status and type 2 diabetes are associated with impaired microvascular reactivity. HRT substantially improves microvascular reactivity in postmenopausal healthy women. In contrast, the effect of HRT on the microvascular reactivity of postmenopausal diabetic women is less apparent.


Birth weight, body mass index and diabetes risk

Title: Intrauterine insemination or in-vitro fertilization in idiopathic subfertility and male subfertility: a randomized trial and cost-effectiveness analysis
Author: R. Lindsay, et al. 
Address: Phoenix, AZ
Source:Diabetes Care 23:1249-1254 (September) 2000

Summary: Researchers hypothesized that, in light of the historical improvements in the management of diabetes during pregnancy, the consequence of offspring of mothers who had diabetes during pregnancy experiencing an increased risk later of diabetes and obesity might be diminishing with time. Birth weight and information of BMI and glucose tolerance were collected as part of an epidemiological survey. Researchers examined this information and diabetes in offspring of mothers with type 2 diabetes during pregnancy born in four ten year time intervals since 1955 and compared with offspring whose mothers either had not developed diabetes or were prediabetic. It was discovered that the offspring of diabetic mothers were heavier at birth, had a higher BMI at all ages throughout childhood, and had an increased incidence rate of diabetes during childhood and as adults. In children born after 1965, despite secular trends to higher BMI and diabetes incidence in the offspring of nondiabetic mothers, differences in BMI and birth weight of offspring of diabetic mothers versus offspring of nondiabetic mothers and offspring of prediabetic mothers appeared to have been maintained. It was concluded that, with the possible exception of those born before 1965, the increased risk of diabetes and obesity experienced by children of diabetic mothers does not seem to be diminishing with time. 
Comment: Very important information.


Definition of hypertension

Title: Hypertension in type 2 diabetes
Source: Clinical Insights in Diabetes Number 19, November 1999

Summary: Hypertension is 1.5-2 times more common in patients with diabetes than in matched individuals without diabetes. Overall, diabetes increases the relative risks of death from coronary heart disease and death from stroke about threefold. The World Health Organization (WHO)-International Society of Hypertension (ISH) reported a substantially lower risk of cardiovascular disease in those who maintained diastolic pressure below 80mm Hg. The WHO-ISH guidelines for blood pressure are: optimal <120/<80; normal <130/<85; high normal 130-139/85-89; grade 1 hypertension 140-159/90-99; grade 2 hypertension 160-179/100-109; grade 3 hypertension >180/>110; isolated systolic hypertension >140/<90. 

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