Glycometabolic Control Research Articles

Overage and overweigh: which is the main determinant of andropause

Systemic testosterone levels fall about 1% each year in men. The reasons of such association are only partially known. A large body of evidence has demonstrated that hypogonadotropic or mixed hypogonadism is closely associated with type 2 diabetes mellitus (T2DM). On the other hand the association between Metabolic Syndrome (MetS) and hypogonadism is emerging. Since MetS is often present in patients with T2DM, we recently evaluated the different contribution of these two conditions in the pathogenesis of male hypogonadism. In a consecutive series of 1134 patients we demonstrated that, diabetes per se, independently of MetS, was not associated with hypogonadism. Alexander et al. has previously reported similar results in predicting CV diseases. The pathogenetic mechanisms involved in this issue are not completely understood, however it could be speculated that some factors associated with visceral adiposity, and upstream of insulin resistance, could contribute both to hypogonadism and CV diseases. Whether or not low testosterone could play a pathogenetic role in CV disease is under debate. However, it should be recognized that meta-analysis reports have clearly demonstrated that testosterone replacement therapy determines a reduction of fat mass and an improvement of lipid profile. Although lifestyle approach and weight loss are characterized by an improvement of CV profile as well as by an increase of testosterone, recently it has been reported that the combination of testosterone therapy and lifestyle approach determine a better outcome in glycometabolic control, weight loss and lipid profile in patients with T2DM.

Exercise and cardiovascular risk reduction: time to update the rationale for exercise?

although it is generally accepted that the promotion of exercise accords with clinical best practice, the anecdotal experience of many primary care physicians, cardiologists, and exercise physiologists is that, even when exercise prescriptions are adhered to, risk factors often fail to demonstrate

Performance characteristics and clinical utility of an enzymatic method for the measurement of glycated albumin in plasma

Objective: The measurement of plasma glycated albumin is particularly useful in the short-middle term monitoring of glycometabolic control in diabetics. The aim of this work is to evaluate a new enzymatic method for the measurement of glycated albumin in plasma, with particular attention to some selected cases and comparison with other relevant tests (fasting plasma glucose, after glucose load, fructosamine, glycated hemoglobin). Design and methods: We have performed a multicenter study by which sample collection was performed in three different centers (Milano, Padova and Cagliari) and serum samples, frozen at − 80 °C, were then delivered under dry ice to the centralized laboratory in Milano. Glycated plasma albumin was measured with reagents from Asahi Kasei Pharma (Lucica GA-L enzymatic assay; AKP, Tokyo, Japan) on a Modular P Roche system. Fructosamine was assessed by a Roche method and HbA 1c (measured separately in the three centers on fresh EDTA blood) by DCCT-aligned HPLC systems. We have investigated 50 type 2 diabetics, 26 subjects with gestational diabetes, 35 subjects with thalassemia major, 10 subjects with cirrhosis, 23 patients with end-stage renal disease subjected to dialysis treatment and 32 healthy adult control subjects. Results: The main analytical performance characteristics of the new GA test were the following: (a) the within-assay reproducibility was between 3.0 and 3.9% (in terms of GA% CV, measured on 2 serum pools and 2 control materials at normal and pathological glycated albumin levels); (b) the between-assays reproducibility was from 2.8 to 4.1%; (c) the linearity was tested in the interval between 13 and 36% and found acceptable ( r 2 = 0.9932). Concerning the clinical utility of the new test, we have evaluated the relationships between GA, HbA 1c, fructosamine and fasting and post-prandial glucose in several patients, as well as the changes in the abovementioned parameters in a sub-group of type 2 diabetic patients for 18 weeks as they progressed from severe hyperglycemia (HbA 1c ≥ 10.0%) toward a better glycemic control. The correlations between glycated albumin and HbA 1c were as follows: (a) type 2 diabetics: r 2 = 0.483 (good glycemic control), r 2 = 0.577 (poor control); (b) diabetic patients under dialysis: r 2 = 0.480; (c) liver disease: r 2 = 0.186; (d) transfused non-diabetics with thalassemia: r 2 = 0.004. Glycated albumin, as well as HbA 1c and fructosamine, was of little value in the study of women with gestational diabetes, mainly because of the very limited glucose fluctuations in this particular category of subjects. In 11 type 2 diabetic patients under poor metabolic control, GA was better correlated with fasting plasma glucose then HbA 1c ( r 2 = 0.555 vs. 0.291, respectively), and decreased more rapidly than HbA 1c during intensive insulin therapy. Conclusions: The experience we have acquired with the new enzymatic test demonstrates its reproducibility and robustness. We confirm that plasma glycated albumin is better related to fasting plasma glucose with respect to HbA 1c. Moreover, glycated albumin is more sensitive than HbA 1c with regard to short-term variations of glycemic control during treatment of diabetic patients. This test is also very appropriate when the interpretation of HbA 1c is critical.

Changes in oxidant-antioxidant status in young diabetic patients from clinical onset onwards.

Oxidative stress has been implicated as a mechanism underlying hyperglycaemia-associated cellular damage and could play a role in the development of diabetes-related complications. This study aimed to evaluate the significance of changes in oxidant–antioxidant status in 176 child and adolescent diabetic patients at clinical onset, during disease progression and when early microvascular complications appeared. Indicative lipid and protein oxidation markers and antioxidant defence activity were measured in plasma and correlated with clinical data, diabetes duration, long-term glycometabolic control and serum lipids. Compared with their respective age-matched controls, diabetic patients had greater oxidative damage to lipids and proteins, demonstrated through the analysis of hydroperoxides, lipoperoxides and oxidation protein products, all of which were significantly raised at onset, decreased during the first 1.5 years of evolution and rose progressively thereafter. Plasma levels of oxidizable lipids were significantly associated with lipid and protein oxidation products. Overall, plasma antioxidant capacity was significantly and consistently lower from clinical onset onwards. These results suggest that insulin therapy in the first year improved metabolic and oxidant homeostasis and consequently hyperglycaemia-derived biomolecular oxidative damage. Diabetes-associated hyperlipidaemia is related to lipid and protein oxidation processes, which supports the concept of glucose toxicity and lipotoxicity being interrelated. The greatest increase in lipid and protein oxidative damage biomarkers in young diabetic patients with premature microangiopathy points to oxidative stress as a possible contributing mechanism of microvascular dysfunction. Consequently, tight lipid and glycometabolic control may have therapeutic potential by diminishing oxidative tissue-damaging effects of hyperglycaemia.

PANCREAS AND ISLET TRANSPLANTATION: CLINICAL INDICATIONS AND CLINICAL RESULTS

Pancreas transplantation is the more effective cure for type 1 diabetes. Although intensive insulin scheme has been demonstrated to reduce the incidence of diabetes related complication, only pancreas transplantation normalizes glycometabolic control, avoids the risk of severe hypoglycemic events and prevents or in some case ameliorates diabetes related complications. In this review it will be analyzed the impact of pancreas transplantation on diabetes related complication and patient survival. Islet cell transplantation has recently emerged as one the most promising therapeutic approaches to improving glycometabolic control in type 1 diabetic patients and, in many cases, to obtaining insulin independence. Islet cell transplantation requires a relatively short hospital stay and has the advantage of being a relatively noninvasive procedure. The rate of insulin independence 1 year after islet cell transplantation has significantly improved in recent years Data from a recent international Trial confirmed that islet cell transplantation can be potentially a cure for type 1 diabetes. Recent data indicate that insulin independence after islet cell transplantation is associated with an improvement in glucose metabolism and quality of life and with a reduction in hypoglycemic episodes. Islet cell transplantation is still in its initial stages, and many obstacles still need to be overcome. Once clinical islet transplantation has been successfully established, this treatment could even be offered to diabetic patients long before the onset of diabetic complications or to patients with life-threatening hypoglycemic unawareness and brittle diabetes.

Eliminating the Diabetic Disadvantage: The Portland Diabetic Project

The Portland Diabetic Project is an ongoing prospective study of 5534 diabetic cardiac surgery patients that elucidates the effects of hyperglycemia, and its subsequent reduction with continuous insulin infusions (CII), on in-hospital outcomes. Increasing glucose levels were found to be directly associated with increasing rates of death, deep sternal wound infections (DSWI), length of stay (LOS), and hospital costs. In separate multivariable analyses, hyperglycemia was found to be independently predictive of mortality (P < 0.0001), DSWI (P = 0.0001), and LOS (P < 0.002). Conversely, CII, designed to achieve predetermined target glucose levels, independently reduced the risks of death and DSWI by 65% and 63%, respectively (P < 0.001 for both). Target glucose levels <150 mg/dL and a 3-day postoperative duration of CII therapy are both important variables that determine the impact of the CII therapy on improved outcomes. Perioperative hyperglycemia in cardiac surgery patients adversely alters mortality, LOS, and infection rates. CII eliminate the increased risks of these complications previously seen in diabetic patients. CII protocols are the standard-of-care for glycometabolic control in cardiac surgery patients.

Effect of Hyperglycemia and Continuous Intravenous Insulin Infusions on Outcomes of Cardiac Surgical Procedures: The Portland Diabetic Project

ObjectiveTo describe the main findings of the Portland Diabetic Project, which elucidates the adverse relationship between hyperglycemia and outcomes of cardiac surgical procedures in patients with diabetes and delineates the protective effects of intravenous insulin therapy in reducing those adverse outcomes. ResultsIn this ongoing 17-year prospective, nonrandomized, interventional study of 4,864 patients with diabetes who underwent an open-heart surgical procedure, we investigated the effects of hyperglycemia, and its subsequent reduction by continuous intravenous insulin (CII) therapy, on in-hospital outcomes. Increasing blood glucose levels were found to be directly associated with increasing rates of death, deep sternal wound infections (DSWI), length of hospital stay (LOS), and hospital cost. In separate multivariate analyses, increasing hyper-glycemia was found to be independently predictive of increasing mortality (P<0.0001), DSWI (P = 0.017), and LOS (P<0.002). Conversely, CII therapy, designed to achieve predetermined target blood glucose levels, independently reduced the risks of death and DSWI by 57% and 66%, respectively (P<0.0001 for both). Target blood glucose levels of less than 150 mg/dL and a 3-day postoperative duration of CII therapy are both important variables that determine the effect of the CII therapy on improved outcomes. Coronary artery bypass grafting-related mortality (2.5%) and DSWI rates (0.8%) in patients with diabetes were normalized to those of the nondiabetic population by the use of the Portland CII Protocol. ConclusionPerioperative hyperglycemia in patients undergoing a cardiac surgical procedure affects biochemical and physiologic functions, which, in turn, adversely alter mortality, LOS, and infection rates. The Portland CII Protocol is a cost-efficient method that effectively eliminates hyperglycemia and reduces postoperative morbidity and mortality in patients with diabetes undergoing an open-heart operation. CII protocols should be the standard care for glycometabolic control in all patients undergoing cardiac surgical procedures. (Endocr Pract. 2004; 10[Suppl 2]:21-33)

Diabetes mellitus and cardiovascular risk: just another risk factor?

Patients with type 2 diabetes are at increased risk of developing cardiovascular disease. Also, individuals with cardiovascular disease have a poorer prognosis if they are diagnosed with type 2 diabetes. The coexistence of these two disorders increases the risk for morbidity and mortality from large- and small-vessel disease. The importance of dysfunctional glucose metabolism is apparent even at the earliest stages of vascular disease, with insulin resistance contributing to or arising from endothelial dysfunction. In the clinical setting, antihypertensive treatment. Produces proportionally greater benefits in patients with type 2 diabetes than in non-diabetic individuals, and treatments that lower blood glucose reduce the risk of cardiovascular complications. As more becomes known about the inter-relationship of glycometabolic control and cardiovascular disease, the aetiology, pathology and treatment of the two diseases are becoming increasingly entwined. The present review summarizes the importance of type 2 diabetes in cardiovascular disease and discusses some of the therapeutic implications that arise from newly emerging data.

Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting

Objective: Diabetes mellitus is a risk factor for death after coronary artery bypass grafting. Its relative risk may be related to the level of perioperative hyperglycemia. We hypothesized that strict glucose control with a continuous insulin infusion in the perioperative period would reduce hospital mortality. Methods: All patients with diabetes undergoing coronary artery bypass grafting (n = 3554) were treated aggressively with either subcutaneous insulin (1987-1991) or with continuous insulin infusion (1992-2001) for hyperglycemia. Predicted and observed hospital mortalities were compared with both internal and external (Society of Thoracic Surgeons 1996) multivariable risk models. Results: Observed mortality with continuous insulin infusion (2.5%, n = 65/2612) was significantly lower than with subcutaneous insulin (5.3%, n = 50/942, P < .0001). Likewise, glucose control was significantly better with continuous insulin infusion (177 ± 30 mg/dL vs 213 ± 41 mg/dL, P < .0001). For internal comparison, multivariable analysis showed that continuous insulin infusion was independently protective against death (odds ratio 0.43, P = .001). Conversely, cardiogenic shock, renal failure, reoperation, nonelective operative status, older age, concomitant peripheral or cerebral vascular disease, decreasing ejection fraction, unstable angina, and history of atrial fibrillation increased the risk of death. For external comparison, observed mortality with continuous insulin infusion was significantly less than that predicted by the model (observed/expected ratio 0.63, P < .001). Multivariable analysis revealed that continuous insulin infusion added an independently protective effect against death (odds ratio 0.50, P = .005) to the constellation of risk factors in the Society of Thoracic Surgeons risk model. Conclusion: Continuous insulin infusion eliminates the incremental increase in in-hospital mortality after coronary artery bypass grafting associated with diabetes. The protective effect of continuous insulin infusion may stem from the effective metabolic use of excess glucose to favorably alter pathways of myocardial adenosine triphosphate production. Continuous insulin infusion should become the standard of care for glycometabolic control in patients with diabetes undergoing coronary artery bypass grafting.J Thorac Cardiovasc Surg 2003;125:1007-21

Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 79

Peripheral neuropathy is one of the most common secondary complications of diabetes mellitus, causing severe and prolonged morbidity. However, clinical and experimental studies have reported that careful glucose control may prevent, stabilize, and/or reverse neuropathy and other chronic diabetic complications. Unfortunately, insulin therapy does not prevent the development or progression of chronic lesions in the vessels, kidneys, eyes, or nerves of the diabetic patient. There is great interest in investigating other forms of endocrine replacement therapy, such as transplantation of the pancreas or of the islets of Langerhans (IT). Diabetic polyneuropathy (DP) evolution is characterized by progressive demyelination and axonal loss and is manifested by signs and symptoms on physical examination and abnormalities in nerve conduction studies (NCS). NCS provide reliable, noninvasive, objective measures of peripheral nerve function and constitute the most important technique for the evaluation of the severity of DP in clinical trials. Several research groups have demonstrated that skin biopsy with measurement of intraepidermal nerve fiber density is another method minimally invasive and repeatable that provides direct pathologic evidence of axonal damage in diabetic neuropathy. Fifty‐one consecutive IDDM patients with or without end stage renal disease were enrolled at the moment of islet (Is), kidney (KD), kidney‐pancreas (KP) or kidney‐islet (KI) transplantation. Patients underwent skin biopsy punch, neurologic examination and neurophysiological investigation. Particularly, 20 pts underwent KP tx, 16 KD tx, 10 islet tx and 5 KI. The patients were comparable for duration of diabetes, dialysis (when present), age, lipid profile. In half of the patients a follow‐up of 2 years has been reached. After KP tx, and partially with KI, a complete normalization of glycometabolic control has been achieved, with statistically lower HbA1c in comparison with KD group (KP = 6.2; 0.1% vs. KD = 8.4; 0.5%; p &lt; 0.01). In the KI/Is group, a long‐term restoration of islet endocrine function has been achieved, with insulin independence. When this has been lost, a persistent secretion of C‐peptide was shown for a long period of time. This was correlated with a global improvement quality of life and vascular structure. Preliminary results will be presented.

Serum Ionized Magnesium Levels in Type 2 Diabetic Patients with Microalbuminuria or Clinical Proteinuria

Background/Aims: The association between microalbuminuria and magnesium depletion is a controversial issue, and serum ionized magnesium levels have not been previously studied in patients with different grades of diabetic nephropathy. Therefore, the aim of this study was to evaluate circulating ionized magnesium concentrations in patients with non-insulin-dependent diabetes mellitus (NIDDM) and incipient or overt diabetic nephropathy. Methods: We measured fasting plasma glucose, creatinine, creatinine clearance estimate, total cholesterol and triglycerides, and serum ionized magnesium (ion-selective electrodes, ISE) in 30 NIDDM patients with urinary albumin excretion rate (UAER) <20 μg/min (normoalbuminuria), 30 NIDDM patients with microalbuminuria (20 < UAER < 200 μg/min), 30 NIDDM patients with clinical proteinuria (UAER >200 μg/min), and 20 healthy subjects. Results: Serum ionized magnesium levels were significantly reduced in diabetic patients when compared to control subjects (0.39 ± 0.06 vs. 0.58 ± 0.05 mmol/l, p < 0.001). Moreover, diabetic patients with microalbuminuria or clinical proteinuria showed a significant decrease in serum ionized magnesium with respect to normoalbuminuria group (normoalbuminuria: 0.45 ± 0.02 mmol/l; microalbuminuria: 0.36 ± 0.05 mmol/l, p < 0.001; clinical proteinuria: 0.35 ± 0.04 mmol/l, p < 0.001). Serum ionized magnesium showed a significant negative correlation with plasma HbA1c and triglycerides in both microalbuminuria and clinical proteinuria groups. Multiple linear regression analysis showed that circulating ionized magnesium levels decrease together with the increase of plasma HbA1c and triglycerides in NIDDM patients with incipient or overt nephropathy, also after adjusting for age, sex, BMI, diabetes duration, systolic and diastolic blood pressure, hypoglycemic therapy, plasma creatinine, creatinine clearance, plasma cholesterol and fasting glucose. Conclusions: Microalbuminuria and clinical proteinuria, as well as poor glycometabolic control and hypertriglyceridemia, are associated to relevant alterations in magnesium metabolism, and the measurement of serum ionized magnesium seems to represent a useful biochemical tool for the study of magnesium disturbances in patients with different grades of diabetic nephropathy.

Cigarette smoking and plasma total homocysteine levels in young adults with type 1 diabetes.

The purposes of this study were to compare plasma total homocysteine (tHcy) levels, a recognized cardiovascular risk factor, in nondiabetic subjects and type 1 diabetic patients, and to evaluate whether chronic cigarette smoking had a deleterious effect on plasma tHcy levels in type 1 diabetic patients. Plasma tHcy concentrations were measured in 60 young type 1 diabetic patients without clinical evidence of macroangiopathy and in 30 healthy control subjects who were matched for age, sex, BMI, and smoking habit. Plasma tHcy levels were significantly higher in type 1 diabetic patients than in control subjects (12.5 +/- 4.8 vs. 10.3 +/- 2.2 micromol/l, P = 0.01). After stratification by smoking status, diabetic smokers had values for age, sex, BMI, lipids, creatinine, blood pressure, glycometabolic control, diabetes duration, and microvascular complications that were superimposable on their nonsmoking counterparts. Nevertheless, plasma tHcy levels were markedly elevated in diabetic smokers versus nonsmokers (15.5 +/- 5.7 vs. 10.6 +/- 3 pmol/l, P < 0.0001) in a dose-dependent fashion (P < 0.0001, by analysis of variance when subjects were categorized for the number of cigarettes smoked daily). Chronic cigarette smoking seems to adversely affect plasma tHcy levels in young adults with type 1 diabetes.

Cigarette smoking and insulin resistance in patients with noninsulin-dependent diabetes mellitus.

To evaluate the effects of chronic cigarette smoking on insulin sensitivity in patients with noninsulin-dependent diabetes mellitus (NIDDM), we examined 28 smokers and 12 nonsmokers with NIDDM, of similar sex, age, body mass index, waist/hip ratio, alcohol consumption, physical activity level, glycometabolic control, diabetes duration, and treatment. Insulin and C-peptide responses to oral glucose load were significantly higher in smokers than nonsmokers, whereas glucose levels were not substantially different. During insulin clamp (20 mU/min.m2), carried out in combination with tritiated glucose infusion and indirect calorimetry, total glucose disposal was markedly reduced in smokers vs. nonsmokers [19 +/- 1.2 vs. 33 +/- 5 mumol/min.kg fat-free mass (FFM); P < 0.001], in a dose-dependent fashion (F = 6.8, P < 0.001 by ANOVA when subjects were categorized for number of cigarettes smoked per day). Oxidative (9 +/- 1 vs. 14 +/- 2 mumol/min.kg FFM; P < 0.01) and nonoxidative (10 +/- 1 vs. 19 +/- 4 mumol/min.kg FFM; P < 0.01) pathways of insulin-mediated intracellular glucose metabolism were similarly reduced in smokers vs. nonsmokers. Plasma free fatty acid levels (240 +/- 33 vs. 130 +/- 23 microEq/L; P < 0.05) and lipid oxidation rate (1.39 +/- 0.1 vs. 0.95 +/- 0.2 mumol/ min.kg FFM; P < 0.05) were less suppressed by hyperinsulinemia in smokers than nonsmokers. In conclusion, chronic cigarette smoking seems to markedly aggravate insulin resistance in patients with NIDDM.

Retrospective analysis of long-term hemorheologic effects of pentoxifylline in diabetic patients with angiopathic complications.

Blood rheology alterations have often been reported in diabetic patients and may be associated with an increased risk for diabetic vascular disease. In this light a hemorheologic approach with pentoxifylline has been suggested in diabetic patients with hemorheological changes in order to improve the hemorheology approach and to evaluate the long-term effects of this treatment on the other clinical and metabolic variables. The study concerned a 10-year retrospective analysis of diabetic patients with hemorheologic alterations and angiopathic complications. Pentoxifylline (Trental 400) significantly reduced blood and plasma viscosity (at high and low shear-rates), fibrinogen and erythrocyte aggregation, and increased erythrocyte filterability throughout the study. The improvement of the hemorheologic pattern was obtained independently of the variation in glycometabolic control and body weight changes, whereas concomitant reductions of arterial blood pressure levels and of urinary excretion of albumin and total proteins was observed during the treatment. Pentoxifylline might therefore be successfully employed for long-term periods in the treatment of hemorheologic disorders in diabetic patients without effects on the metabolic pattern.

Serum lipoprotein-a levels and glyco-metabolic control in insulin and non-insulin dependent diabetes mellitus

Objectives: Conflicting results for lipoprotein-a (Lp(a)) levels in diabetic patients exist in the literature. Normal, increased, and decreased values are described, and a relation to glycometabolic control is not unequivocally established. Design and Methods: In our study Lp(a) was measured in a large group of diabetics (80 patients with IDDM and 90 patients with NIDDM) in relation to glycometabolic control and the presence of microalbuminuria, retino and/or neuropathy. Long-term and short-term glycometabolic control were assessed by HbA1 and fructosamine assays, respectively. Results: Statistically significant differences between Lp(a) levels in IDDM and NIDDM and a control group of 110 healthy nondiabetics could not be established. It appeared that the level of Lp(a) in IDDM and NIDDM is independent of short-term and long-term glycometabolic control or the occurrence of microalbuminuria, neuro or retinopathy. However, poor glycometabolic control affected the number of Lp(a) levels elevated above a threshold of 0.25 g/L in IDDM. Conclusion: These results suggest that the level of Lp(a) in serum is not influenced by diabetes imellitus, glycemic control, or the occurrence of microalbuminuria, neuro or retinopathy.

Glycosylated hemoglobin and fructosamines: does their determination really reflect the glycemic control in diabetic patients?

The present experiment was designed to determine whether scavenging capacity of serum, in addition to glucose level, influences hemoglobin and serum protein glycosylation in non-insulin dependent diabetic patients. For this purpose fortyseven patients homogeneous for age, disease duration, therapy and glyco-metabolic control were selected Fasting and post-prandial glycemia and insulinemia as well as glycosuria were weekly analysed during the sixty days preceding glycosylated hemoglobin (HbA1c), fructosamines and serum scavenging capacity determination. This last parameter has been evaluated by a method based on the property of β-phycoerythrin (β-PE) to loss its fluorescence when damaged by oxygen radicals, that were produced by Cu ++ and H 2C 2. The oxygen radical absorbance capacity (ORAC OH) of serum was assayed as the ability of serum to delay the loss of β-PE fluorescence. As expected, a statistically significant positive correlation was found comparing both fructosamines and HbA1c levels with mean fasting glycemia measured over twenty and sixty days, respectively. The key result of this study is represented by the finding that both HbA1c and fructosamines levels show a statistically significant negative correlation with ORAC OH values. This correlation can explain a large percent of the data dispersion occurring when ORAC OH is not taken into account. In order to better describe the role of ORAC OH, patients were separated into two sub-groups with an ORAC OH lower (L-ORAC OH) and greater (H-ORAC OH) than 100 U/ml. Examining the correlation between mean fasting glycemia and the two glycosylated proteins considered in these two sub-groups, curves with different slopes were obtained, supporting that the rate of glycosylation of both proteins was higher in L-ORAC OH patients as compared to those with HORAC OH. Present data suggest that for a proper interpretation of the HbA1c and fructosamines data in diabetic patients, the scavenging capacity level of serum should be taken into account

Contraception guidance in women with pre-existing disturbances in carbohydrate metabolism

To review our studies on the clinical and metabolic impact of contraceptive methods in women with insulin dependent diabetes mellitus (IDDM) and women with previous gestational diabetes mellitus (GDM) in order to provide suggestions for the contraceptive counselling of these women. The clinical events following first insertions of copper IUDs were studied in 103 women with IDDM and in 119 non-diabetic women. Moreover we studied the effects on glycometabolic control and lipid metabolism in women with well-controlled IDDM using low-dose oral contraceptives (OCs) containing ethinylestradiol combined with norethisterone (n = 10), levonorgestrel (n = 9) or gestodene (n = 11). Hemostatic and endothelial function was also studied in the women using the gestodene-containing preparation. Finally, we studied the impact of oral contraceptives on the insulin sensitivity in women with previous GDM. The continuation rates and indications for medical removal of the IUDs were similar in the diabetic and the non-diabetic women. There was no increased pregnancy rate or increased frequency of pelvic inflammatory disease in the diabetic women. The glycemic control was not changed by the OCs and none of the treatment regimens were associated with changes in plasma lipids linked to increased risk of atherosclerosis. Indications of increased fibrin formation, which seemed to be compensated by increased fibrinolytic activity, were noted with the gestodene-containing preparation. None of the women developed microalbuminuria during the study. Compared to normal women, we found reduced insulin sensitivity in the women with previous GDM using the pill. Intrauterine devices and barrier methods can be used by diabetic women with the same reservations as in the general population. Low-dose OCs do not influence the glycemic control and have no adverse impact on plasma lipids. The balance between fibrin formation and resolution was maintained during intake of the gestodene-containing pill. Our findings suggest that combined oral contraceptives can be used in women with uncomplicated IDDM and in women with previous GDM if clinical and metabolic monitoring can be ensured.

Oral contraceptives and diabetes mellitus

Objectives: A review of the metabolic effects of oral contraceptives (OCs) in women with insulin-dependent diabetes mellitus (IDDM) and previous gestational diabetes mellitus (GDM).Methods: The effects on glycometabolic control and lipid metabolism were studied in women with well controlled IDDM using low-dose OCs containing ethinyl estradiol combined with norethisterone, levonorgestrel or gestodenc. The hemostatic and endothelial function was also studied in the diabetic women using the gestodene-containing preparation. In women with previous GDM, investigations on insulin sensitivity were performed during intake of a triphasic lowdose oral contraceptive with levenorgestrel.Results: In women with IDDM the glycemic control was not changed by the OCs and none of the treatment regimens were associated with changes in plasma lipids linked to increased risk of atherogenesis. Analysis of the hemostatic balance during intake of the gestodene-containing preparations gave indication of increased fibrin formation which seemed to be compensated by increased fibrinolytic activity. None of the women developed niicroalbutninui-ia during the study. Compared to normal women, reduced insulin sensitivity was found in women with previous GDM using the combined pill.Conclusion: Low-dose OCs do not influence the glycemic control and have no adverse impact on plasma lipids. The balance between fibrin formation and resolution was maintained during intake of- the gestodene-containing pill. Our findings suggest that combined oral contraceptives can be used in women with uncomplicated IDDM and in women with previous GDM if clinical and metabolic monitoring can be ensured to detect progression to frank diabetes.

Hormonal Contraception in Women With IDDM: Influence on glycometabolic control and lipoprotein metabolism

Safe and effective contraceptive methods are essential for women with insulin-dependent diabetes mellitus (IDDM), but opinions on the use of hormonal oral contraceptives by these women are conflicting. We evaluated the effects on glycometabolic control and lipoprotein metabolism in women with IDDM treated with an oral contraceptive not previously studied in a diabetic population. A total of 22 women with IDDM received a monophasic combination of ethinyl estradiol and gestodene for 1 year; 20 women of comparable diabetic status using nonhormonal contraception were selected as control subjects. Evaluation was performed before and after 1, 3, 6, and 12 months of hormonal intake using nonparametric statistical methods. Except for a higher median age of the control group, the baseline values for all clinical and metabolic variables were similar in the two groups, and in neither of the groups were changes in blood pressure, body mass index, or glycemic control observed. In the oral contraceptive group, decreased serum levels of low-density lipoprotein (LDL) cholesterol and increased levels of triglycerides and lipoprotein A were noted, whereas total cholesterol and high-density lipoprotein cholesterol levels were unchanged. In the control group, a decrease of LDL cholesterol was observed. No effect of tobacco smoking on glycometabolic control or lipoprotein metabolism could be demonstrated during hormonal intake. No evidence of impaired glycometabolic control or adverse changes in serum levels of lipoproteins known to be associated with atherosclerosis was observed in women with well-controlled IDDM during 1 year of oral contraception with ethinyl estradiol and gestodene.

Glycometabolic control, lipids, and coagulation parameters in patients with non-insulin-dependent diabetes mellitus.

Diabetes mellitus and hyperlipidemia are associated with coronary heart disease and with hypercoagulability, another independent risk factor for coronary heart disease. In 65 non-insulin-dependent diabetes mellitus patients [41 females, 24 males, median age 66 years (range 43-81 years)] treated with antidiabetic agents glycometabolic control (HbA1c), lipids (Quetelet index and blood lipids), and several coagulation parameters were studied in comparison with a reference group. Serum triglycerides were elevated [median (interquartile range) 2.3 (1.3) mmol/l vs. 1.6 (0.7) mmol/l in the controls (P < 0.001)], whereas the median lipoprotein(a) concentration was 65 (157) mg/l in the diabetic patients versus 44 (114) mg/l in the control group (not significantly different). Median high-density lipoprotein-cholesterol concentrations were slightly decreased in the diabetic patients: 1.2 (0.3) mmol/l compared with 1.3 (0.4) mmol/l in the control group (P < 0.02). Elevated levels of fibrinogen, fibrin monomers, thrombin-antithrombin III complex, and factor VIIIc were found in the diabetic patients and factor VII in male diabetic patients. These elevated coagulation parameters are indicators of an activated coagulation system in this patient group. By Spearman's rank test, only HbA1c values correlated with anti-thrombin III (r = 0.27, P < 0.03) and showed a tendency towards a correlation with lipoprotein(a) (r = 0.23, P < 0.07). Triglycerides correlated with the Quetelet index (r = 0.27, P < 0.03), high-density lipoprotein-cholesterol (r = -0.41, P < 0.001), and factor VII (r = 0.35, P < 0.01), whereas serum cholesterol concentrations correlated with factor VII (r = 0.27, P < 0.04) and with fibrin monomers (r = 0.29, P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)