All About Diabetes in Women
 
Postprandial Glucose and Cardiovascular Disease (CVD) risk
In people with type 2 diabetes, macrovascular disease, in particular CVD is the major source of morbidity and mortality. Having diabetes increases the risk for CVD mortality more than two-fold
Latest news on Diabetes in Women
Here we have covered latest topics such as…. Risk of recurrent acute lower urinary tract infections in women with and without diabetes, The association between metabolic abnormality and endometrial cancer: a large case-control study, & Increased risk of vertebral fractures independent of BMD or diabetic complications in diabetic patients.
Role of alpha-glucosidase inhibitors (AGIs) in the prevention of type 2 diabetes mellitus
The alpha-glucosidase inhibitors are competitive, reversible inhibitors of alpha-amylase from the pancreas and alpha-glucosidase, which is found in the brush border of the small intestine. This inhibition results in reduced postprandial increases in blood glucose levels by delaying the digestion of dietary carbohydrates.
 
Postprandial Glucose and Cardiovascular Disease (CVD) risk

In people with type 2 diabetes, macrovascular disease, in particular CVD is the major source of morbidity and mortality. The pathogenesis of CVD is complex and multifactorial. Smoking, obesity, dyslipidemia, and hypertension were considered the major “traditional” risk factors. Now diabetes itself is considered an important independent risk factor. Having diabetes increases the risk for CVD mortality more than two-fold.
Ajikumar V Aryangat et al. Vascular Health and Risk Management 2010:6 145–155

Numerous prospective epidemiological studies have demonstrated a correlation between CVD risk and postprandial glucose excursions. Studies confirming putative association between PPG excursion and CVD risk are summarized in (Table 1).
Table 1. Studies Linking Postprandial Glucose Excursions with Risk of CVD and All-Cause Mortality
Study Subjects
(n) 		Follow Up
(Years)		 Findings
Coutinho et al. (meta analysis) 95783 12 Progressive relationship between FPG & 2h glucose & CVD- no threshold.
DECODE 25364 10 High 2h post-load glucose is associated with increased risk of death, independent of FPG.
Helsinki Policeman Study 631 20 1h and 2h OGTT glucose predicted incidence CHD better than FPG.
Honolulu Heart Programme 8006 20 Increased risk gradient between 1h glucose CHD.
Chicago Heart Study 12220 22 1h post load hyperglycaemia-increased mortality in both whites and blacks.
Balkau et al. (meta-analysis) 17000 20 2h post-challenge hyperglycaemia associated with increased all-cause and CVD mortality.

Islington Diabetes Survey

223 obs* 2h glucose- better predictor of CHD than HbA1c
Hoom Study 2363 8 2h glucose-better predicts morality than HbA1c & increases CVD mortality by 62%
Rancho Bernardo Study 1858 7 2h post-challenge glucose > doubles the risk fatal CVD and heart disesase in order adults.
Shaw et al. 9179 5-12 Isolated post-challenge hyperglycaemia risk of mortality.
Diabetes Intervention Study 984 11 Postprandial but not fasting glucose is associated with CVD & all cause mortality
Framingham Offspring study 3370 1 2h glucose predicts CVD events better than HbA1c.
Funagata Diabetes Study 2651 7 IGT- a risk factor for CVD but not IFG.
Cardiovascular Health Study 4515 8 Subjects with IGT- 22% increased risk of CVD compared with NGT subjects.
NHANES 11 Mortality Study 3174 12-16 RR for death from CVD-20% more in IGT &~70% in previously undiagnosed T2 DM.
RIAD study 785 obs* 2h post-challenge hyperglycaemia but not FPG-significant determinant of carotid IMT.
*observation studies
Thus, the compelling clinical evidence linking PPG and CVD, suggests that PPG is a legitimate therapeutic target in the management of the patient with T2DM.
Raj Peter et al. Current Vascular Pharmacology, 2009, 7, 68-74
 
ADA, IDF, and AACE recommendations

The ADA in its Standards of Medical Care in Diabetes–2009 acknowledges that elevated PPG values are associated with increased CV risk – independent of FPG – and that the relative contribution of postprandial hyperglycemia to HbA1c is greater at HbA1c levels that are closer to 7%.

The ADA recommends that individuals who have preprandial glucose values within target, but have HbA1c values above target, should monitor PPG 1 to 2 hours after the start of a meal. Treatment aimed at reducing PPG values to <10 mmol/L (<180 mg/dL) will likely lower HbA1c and may improve outcomes.

The International Diabetes Federation (IDF) recommends that patients with diabetes manage their HbA1c levels to be <6.5% by addressing both FPG and PPG. The guidelines recommend that PPG levels not exceed 7.8 mmol/L (140 mg/dL) during the 2 hours postmeal.

AACE guidelines are similar to those of the IDF, suggesting HbA1c <6.5%, FPG 6 mmol/L (<110 mg/dL), and 2-hour PPG <7.8 mmol/L (<140 mg/dL).
Ajikumar V Aryangat et al. Vascular Health and Risk Management 2010:6 145–155
Effect of fasting plasma glucose (FPG) and two- hour postprandial plasma glucose (2hpp) levels on HbA1c
bullet   A descriptive, cross-sectional study; 300 patients were enrolled.
bullet   All studied patients were diagnosed type 1 or 2 diabetes mellitus.
bullet   Sampling was performed
bullet   FPG and 2hpp plasma glucose were assessed at baseline and at every two weeks to one month-as needed.
bullet   HbA1c was assessed at the end of study.
Results (analyzed by Pierson Covariance and Multiple Regression methods):
bullet   The mean plasma glucose in three groups of HbA1c (good to fair) were 148.5 ± 56.80 mg/dl at fasting, and 199.70 ± 53.01 mg/dl at two hours after breakfast (2hpp) and mean concentration of HbA1c were 8.41 ± 1.1 %.
bullet   The plasma glucose level and HbA1c were 0.312 for fasting and, 0.416 for 2hpp at covariant value.
    Haddadinezhad S et al. Int J Diab Dev Ctries 2010;30:8-10
The postprandial plasma glucose has closer association to glycosylated hemoglobin than fasting plasma glucose
 
Post-prandial hyperglycemia is an important predictor of the incidence of diabetic microangiopathy in type 2 diabetic patients.

Diabetic microangiopathy is often observed in diabetic patients, but there is little evidence regarding the relationship between post-prandial glycemia or insulinemia and the incidence of diabetic microangiopathy.

A cross-sectional study of 232 subjects with type 2 diabetes mellitus who were not being treated with insulin injections was performed to elucidate the relationship between post-prandial glycemia (or insulinemia) and diabetic microangiopathy.

A multiple regression analysis showed that post-prandial hyperglycemia independently correlated with the incidence of diabetic retinopathy and neuropathy. Post-prandial hyperglycemia also correlated, although not independently, with the incidence of diabetic nephropathy. In addition, interestingly, post-prandial hypoinsulinemia independently correlated with the incidence of diabetic retinopathy.

Shiraiwa T et al. Biochem Biophys Res Commun. 2005 Oct 14;336(1):339-45.
Latest news on Diabetes in Women
Risk of recurrent acute lower urinary tract infections in women with and without diabetes
In an exploratory retrospective study involving 7063 women aged >/=30 years, Gorter KJ et al. studied the incidence of recurrent UTI (relapses and reinfection) in women with (n = 340) and without diabetes (n = 6618).
 
bullet   Relapses and reinfections were reported in 7.1% and 15.9% of women with diabetes versus 2.0% and 4.1% of women without diabetes.
bullet   There was an independent higher risk of recurrent UTI in women with diabetes compared with women without diabetes (OR 2.0; 95% CI 1.4-2.9).
bullet   Women taking oral blood glucose-lowering medication (OR 2.1; 95% CI 1.2-3.5) or insulin (OR 3.0; 95% CI 1.7-5.1) or who had had diabetes for >/=5 years (OR 2.9; 95% CI 1.9-4.4) or who had retinopathy (OR 4.1; 95% CI 1.9-9.1) were at risk of recurrent UTI.
Women with diabetes >/=5 years or with glucose-lowering medication or with retinopathy have an increased risk of recurrent UTI.
Gorter KJ et al. Fam Pract. 2010 May 12. [Epub ahead of print]
The association between metabolic abnormality and endometrial cancer: a large case-control study

A large case-control study including 942 endometrial cancers and 1721 controls was conducted on a Chinese population. The relative endometrial cancer risks from various factors were calculated by the x (2) test. Menopausal status and BMI were applied as potential confounders to analyze the joint effects with other factors.
 
RESULTS:
bullet   Overweight/obesity, hypertension, diabetes mellitus and glucose metabolic disturbance were all associated with endometrial cancer risk.
bullet   Effective medication on diabetes can significantly decrease cancer risk (uncontrolled diabetes: RR=5.563, 95% CI=2.406-12.859, p<0.001; controlled diabetes: RR=1.331, 95% CI=0.529-3.352, p>0.05) as compared with normal controls.
bullet   Serum lipids were also found to be linked to endometrial cancer risk
bullet   Positive correlations were present with total serum cholesterol, triglycerides, low-density lipoprotein cholesterol and dyslipidaemia, while
bullet   A negative correlation was found with high-density lipoprotein cholesterol.
bullet   An elevated risk for type I endometrial cancer (OR=1.839, 95% CI=1.539-2.197, p<0.001) in women with BMI>or=24.58 versus those with BMI<24.58, but not for type II cancer (OR=1.092, 95% CI=0.969-1.231, p>0.05).
    Zhang Y et al. Gynecol Oncol. 2010 Apr;117(1):41-6.
Diabetic patients have an increased risk of vertebral fractures independent of BMD or diabetic complications.
Although patients with type 2 diabetes (T2DM) have an increased risk of hip fracture, risk of vertebral fracture (VF) and its association with BMD are still unclear. Japanese T2DM patients (161 men >50 yr and 137 postmenopausal women) and non-DM controls (76 and 622, respectively) were examined by lateral spine radiography and DXA at the lumbar spine (L), femoral neck (FN), and radius (R).

Logistic regression analysis adjusted for age, body mass index, and L-BMD showed that
bullet   The presence of T2DM was an independent risk factor for prevalent VFs in women (OR = 1.86, p = 0.019) and men (OR = 4.73, p < 0.001).
bullet   BMD at any site, however, was not significantly associated with the presence of prevalent VFs in T2DM patients, in contrast to the significant association in controls (at least p = 0.010).
bullet   Comparison of T2DM patients with and without VFs showed no significant differences in BMD values, bone markers, or diabetes status.
bullet   Receiver operating characteristic analysis showed that the absolute L-, FN-, and R-BMD values for detecting prevalent VFs were higher in T2DM patients than controls, whereas their sensitivity and specificity were lower.
bullet   T2DM patients may have an increased risk of VFs independent of BMD or diabetic complication status, suggesting that bone quality may define bone fragility in T2DM.
    Yamamoto M et al. J Bone Miner Res. 2009 Apr;24(4):702-9.
Role of alpha-glucosidase inhibitors (AGIs) in the prevention of type 2 diabetes mellitus

The alpha-glucosidase inhibitors are competitive, reversible inhibitors of alpha-amylase from the pancreas and alpha-glucosidase, which is found in the brush border of the small intestine. This inhibition results in reduced postprandial increases in blood glucose levels by delaying the digestion of dietary carbohydrates.
http://www.medscape.com/viewarticle/426921

AGIs reversibly inhibit a number of alpha-glucosidase enzymes (eg, maltase), consequently delaying the absorption of sugars from the gut. In a study among healthy subjects it was

suggested that the therapeutic effects of AGIs are not only based on a delayed digestion of complex carbohydrates, but also on metabolic effects of colonic starch fermentation. AGIs might be a reasonable option as first-line drug in the treatment of patients with DM2 as it specifically targets postprandial hyperglycemia, a possible independent risk factor for cardiovascular complications. AGIs are expected to cause no hypoglycemic events or other life-threatening events, even at overdoses, and cause no weight gain.
Floris Alexander van de Laar et al. Vascular Health and Risk Management 2008:4(6) 1189–1195

Any intervention in the impaired glucose tolerance phase that reduces resistance to insulin or protects the beta-cells, or both, should prevent or delay progression to diabetes. Voglibose acts by competitively inhibiting the alpha-glucosidases, a group of key intestinal enzymes involved in the digestion of carbohydrates. They decrease both postprandial hyperglycaemia and hyperinsulinaemia, and thereby may improve sensitivity to insulin and release the stress on beta-cells. These compounds do not induce hypoglycaemia and have a good safety profile.
Scheen AJ. Et al. Drugs. 2003;63(10):933-51.
Combination therapy with mitiglinide and voglibose improves glycemic control in type 2 diabetic patients on hemodialysis.
An open-label randomized study with 36 type 2 diabetics with poor glycemic control on HD and receiving daily doses of voglibose (0.9 mg) was performed. The patients were randomly assigned to two groups:
bullet   Combination-therapy group (mitiglinide group), mitiglinide initial dose 7.5 - 15 mg titrated to 30 mg daily and constant daily dose 0.9 mg of voglibose, and
bullet   Monotherapy group (control group), constant daily dose 0.9 mg of voglibose alone.
 
The efficacy of the treatment was determined by monitoring plasma glucose, hemoglobin A1c (Hb(A1c)), and glycated albumin (GA) levels and using homeostasis model assessment of insulin resistance (HOMA-IR). Safety and tolerance were determined by monitoring clinical and laboratory parameters.
The final dose of mitiglinide was 22.9 +/- 8.9 (mean +/- s.d.) mg (0.41 mg/kg) daily. Mitiglinide and voglibose combination reduced fasting plasma glucose and GA levels after 4 weeks and Hb(A1c) levels after 8 weeks. Triglyceride levels and HOMA-IR values also decreased significantly after combination treatment. No significant changes in blood pressure levels or serious adverse effects such as hypoglycemia or liver impairment were observed.

This study suggests a combination therapy of mitiglinide and voglibose may have potential for the treatment of diabetics on HD.
Abe M et al. Expert Opin Pharmacother. 2010 Feb;11(2):169-76.