Blood glucose levels in diabetic and non-diabetic subjects

1989 Claude Bernard Lecture of the European Association for the Study of Diabetes delivered in Lisbon on September 1989     

Increments in circulating homocysteine before and after coronary artery bypass surgery in diabetic and non-diabetic patients

This study aims to assess total plasma homocysteine levels in diabetic and non-diabetic patients who underwent coronary artery bypass grafting (CABG) and to determine the effect of cardiopulmonary bypass (CPB) on homocysteine levels. Twenty diabetic and twenty non-diabetic patients who had CABG were enrolled in the study. Plasma samples for the assays were obtained before and after the CPB and on sixth day following the operation. Diabetic patients seemed to have higher levels of plasma total homocysteine in pre-CPB, post-CPB, and postoperative sixth day blood samples. There was a significant difference in total homocysteine levels between pre-CPB and post-CPB both in diabetic and non-diabetic patients. Although an association between the preoperative plasma total homocysteine levels and the frequency of 1-year graft occlusion could not be demonstrated, our data claims attention to the increased homocysteine levels during CPB, which sustained until the sixth day after the surgery.     

Fasting plasma cyclic AMP levels in an adult diabetic and non-diabetic group

Summary Fasting plasma cyclic adenosine monophosphate (cAMP) was measured in 50 matureonset diabetic patients and in 111 non-diabetic patients. Methods used to determine plasma cAMP are described. The addition of sepharose agar beads to the bovine adrenocortical binding protein has considerably improved the sensitivity and simplified the radioligand-receptor assay of cAMP. No statistical differences in plasma cAMP were noted in relation to sex in either group, to the presence of diabetes mellitus, or to age or weight in the non-diabetic patients. Plasma cGMP levels are now being studied to determine if these may prove better indicators of insulin activity than plasma cAMP.     

A comparative study of thyroid hormone levels in young diabetic and non-diabetic patients

Thyroid disorders can adversely affect diabetes control. The aim of the study was to compare thyroid hormone levels in type 1 diabetic patients with that of non-diabetic patients. Fifty two type 1 Diabetic patients were consecutively selected from among those attending the outpatient department of Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorder (BIRDEM) hospital. Fifty three healthy non-diabetic volunteers were selected from the students of a university. Both groups were below 30 years of age. The patients with type 1 diabetes have significantly lower serum FT3 levels (P <0.001) when compared to the control groups. There was no significant difference between controls and study subjects in terms of serum FT4 (P?=?0.376) and TSH (P?=?0.821) concentration. We conclude that alteration of FT3 is a common feature in these subjects with type 1 diabetes mellitus.     

血浆同型半胱氨酸与2型糖尿病外周神经病变的相关性

目的 探讨血浆总同型半胱氨酸浓度与糖尿病外周神经病变的关系.方法 入选2型糖尿病患者227例,进行横断面研究.用临床表现及肌电图诊断外周糖尿病神经病变,并测定血浆同型半胱氨酸水平及与糖尿病神经病变相关或可能影响血浆同型半胱氨酸水平的指标.结果 糖尿病外周神经病变患者80例,糖尿病无神经病变者147例.糖尿病神经病变组血浆总同型半胱氨酸水平(12.6±3.6)μmol/L,高于糖尿病非神经病变组(8.2±0.9)μmol/L(P＜0.01).在校正外周神经病变传统危险因素(糖尿病病程、糖化血红蛋白)及高同型半胱氨酸浓度的影响因素(年龄、性别、血清叶酸和维生素B12、肾功能状态和双胍类使用)后,同型半胱氨酸与糖尿病神经病变仍相关[OR1.15(1.02～1.28),P＜0.05].在校正每单位上述混杂因素增加后,每增加4.0 μmol/L的血浆同型半胱氨酸也与神经病变发生密切相关[OR 1.17(0.94～1.33),P＜0.05].结论 高血浆总同型半胱氨酸浓度与糖尿病神经病变的发生相关,为糖尿病外周神经病变的独立危险因素.

Abstract：

Objective To explore the relationship between plasma homocysteine levels and diabetic peripheral neuropathy (DPNP). Methods A crossectional analysis was conducted on 227 patients with type 2 diabetes. Peripheral neuropathy was confirmed using electromyography (EMG). The risk factors possibly associated with diabetic neuropathy or plasma homocysteine levels were analyzed in relation to likelihood of occurrence of DPNP. Results Eighty patients with neuropathy and 147 patients without neuropathy were included. Plasma homocysteine levels were significantly higher in patients with diabetic neuropathy [( 12. 6 ± 3.6 ) μmol/ L] than without diabetic neuropathy [( 8. 2 ± 0. 9 ) μmol/L] ( P ＜0. 001 ), and the relationship remained significant after adjusting for duration of diabetes, glycosylated hemoglobin A1c (HbA1c), age, renal status, serum folate acid and vitamin B12, and metformin [OR 1.15( 1.02-1.28 ) ,P ＜ 0. 05]. In addition, per increase of 4. 0 μmol/L plasma homocysteine was closely related to the occurrence of neuropathy after controlling for per unit increase of other confounding factors [OR 1.17(0. 94-1.33), P ＜ 0. 05]. Conclusions Hyperhomocysteinemia was an independent risk factor for the occourence of diabetic peripheral neuropathy.     

Glycosylation of maternal hair and cord skin during pregnancy in diabetic and non-diabetic women

A study of 15 insulin-dependent diabetics (IDD), 4 gestational diabetics (GDM), and 21 non-diabetic women was undertaken to assess non-enzymatic glycosylation in maternal hair, cord skin, and cord blood. Glycosylation of maternal hair was stable from tip to root in controls. In the IDD group, levels were highest at the tip, but were significantly lower in the middle and scalp segment (p less than 0.01), both tip and middle segments were higher than control values (p less than 0.01). In contrast, only the scalp segment of hair from the GDM group had a higher than normal level of glycosylation (p less than 0.01). Cord skin and cord blood glycosylation were significantly increased in the IDD group compared with normal (0.100 +/- 0.002 vs 0.074 +/- 0.008 mumol fructosamine/100 mg, p less than 0.01, and 0.160 +/- 0.002 vs 0.14 +/- 0.008, p less than 0.05, mean +/- S.E.M.), respectively. Only cord skin glycosylation was increased in the GDM group (0.116 +/- 0.003, p less than 0.01). Thus near normal glycaemic control of maternal insulin-dependent diabetes during pregnancy was associated with small but significant increases in cord skin glycosylation and a fall towards normal in maternal hair glycosylation which may provide a useful retrospective index of diabetic control.     

Correlations between homocysteine levels and atherosclerosis in Japanese type 2 diabetic patients

Elevated total plasma homocysteine (tHcy) level and aortic stiffness are associated with high mortality in type 2 diabetic patients. We tested the hypothesis that tHcy correlates with aortic stiffness and insulin resistance in type 2 diabetic patients. The study consisted of 40 Japanese patients with type 2 diabetes mellitus and high tHcy levels (mean age +/- SD, 57 +/- 7 years) and a control group of 45 age-matched patients with normal tHcy levels (mean age +/- SD, 57 +/- 6 years). Brachial-ankle pulse wave velocity (BaPWV) was measured by an automatic oscillometric method. Brachial-ankle pulse wave velocity was used as an index of atherosclerosis. Body mass index values (P < .05), waist circumferences (P < .05), and the waist-to-hip ratios (P < .05) were larger in the high-tHcy group than in the normal-tHcy group. The BaPWV was higher in the high-tHcy group than in the normal-tHcy group (P < .0001). Fasting plasma glucose (P < .005) and insulin concentrations (P < .0001), and the homeostasis model assessment (HOMA) index (P < .0001) were higher in the high-tHcy group than in the normal-tHcy group. Multiple regression analysis showed that tHcy levels were independently predicted by BaPWV and the HOMA index. In conclusion, our results indicate that the elevated level of tHcy in Japanese patients with type 2 diabetes mellitus is characterized by increased aortic stiffness and insulin resistance, and that the BaPWV and the HOMA index are independent predictors of tHcy.     

Strontium ranelate decreases plasma homocysteine levels in postmenopausal osteoporotic women

We analyzed the effect of strontium ranelate treatment on plasma homocysteine (Hcy) levels in postmenopausal osteoporotic women. Forty-nine postmenopausal women diagnosed with osteoporosis with a mean age of 54.07 +/- 7.5 years (range 40-70) who visited our menopause clinic were participated in this prospective study. Patients with bone mineral density (BMD) at least 2.5 SD below the average value in young adults (T score < -2.5) were considered to have osteoporosis. Patients received strontium ranelate 2 g/day (Servier) orally with additional calcium supplements. Fasting plasma Hcy levels were assessed at baseline, 3, 6 and 12 months of the therapy with strontium ranelate. The mean plasma Hcy level (10.45 micromol/l) after 3 months of therapy was significantly lower compared to the basal plasma Hcy level (12.61 micromol/l) (P = 0.002). The plasma homocysteine level (10.54 micromol/l) of the 43 patients that were present at the 6 months of the therapy was also significantly lower compared to the basal plasma Hcy level (P = 0.005). At the end of the 12 months of the study, there were 42 patients. The plasma homocysteine level (10.107 micromol/l) at 12 months of therapy was also significantly lower compared to the basal Hcy level (P < 0.001). Strontium ranelate 2 g/day treatment for 1 year significantly decreases plasma Hcy levels in postmenopausal women with osteoporosis. Since the increased Hcy levels could lead to an increase risk of osteoporosis and fracture risk, this effect of strontium ranelate on Hcy level may cause additional benefit in terms of reducing the risk of fracture.     

Differences in the association between glycemia and uric acid levels in diabetic and non-diabetic populations

AimsOur study aimed to investigate the influence of different glycemic statuses and their fasting plasma glucose/2-hour post-load glucose on uric acid level.MethodsA total of 14,787 subjects were recruited after excluding subjects with medication for hyperuricemia or diabetes. Fasting plasma glucose (FPG), 2-hour post-load glucose (2hPG), and uric acid (UA) were measured. Then, subjects were divided into normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes.ResultsAfter adjustment for clinical variables, in NGT group, there was no significant relationship found between UA level and FPG. However, there was a positive association between UA level and 2hPG (β = 0.003, 95% CI: 0.002~0.004). A similar trend was also observed between UA level and 2hPG in IFG group (β = 0.004, 95% CI: 0.000~0.009) and IGT group (β = 0.005, 95% CI: 0.002~0.008), but relationship between UA level and FPG remained insignificant. In diabetes group, UA level was negatively associated with both FPG (β = ?0.008, 95% CI: ?0.010 ~ ?0.007) and 2hPG (β = ?0.005, 95% CI: ?0.006 ~?0.003).ConclusionsIn non-diabetic individuals, UA level increased with 2hPG, but not with FPG, and UA level was inversely associated with both FPG and 2hPG in diabetic population.     

Infective endocarditis in diabetic and non-diabetic patients

We compared clinical, microbiological, and prognostic characteristics of infective endocarditis in patients with and without diabetes mellitus. In 1987--1996, 213 patients with definite or possible infective endocarditis were included, of which 39 (18%) had diabetes mellitus. Diabetic patients were older than non-diabetic (median age of 71 vs 65 y, respectively; p =0.04), had more aortic valve and less mitral valve involvement (71% vs 27%, and 21% vs 62%; p = 0.004). There was no significant difference in the frequency of Staphylococcus aureus involvement between the 2 groups (21% in diabetic vs 20% in non-diabetic group; p = ns). On multivariate analysis diabetes mellitus was not found to be an independent factor for mortality. Unlike other infections diabetes mellitus does not significantly affect clinical and microbiological features, and outcome of infective endocarditis.     

Coagulation in diabetic and non-diabetic claudicants.

BACKGROUND: In order to compare hemostasis in diabetic and non-diabetic claudicants we evaluated endothelial (von Willebrand factor, vWF), rheologic (fibrinogen, hematocrit), coagulation system (thrombin-antithrombin complex, TAT) and platelet (platelet factor 4, PF4, aggregation on thrombin, collagen and ADP stimulation) parameters in both groups and healthy controls. METHODS: Twenty-five diabetic, 34 non-diabetic patients with claudication and 26 healthy individuals were enrolled into the study. RESULTS: The severity of lower limbs ischemia was similar in two groups of claudicants but coronary heart disease and cerebral ischemia were significantly more common in diabetic than in non-diabetic claudicants. vWF level was significantly higher in diabetic than non-diabetic claudicants and healthy controls (184+/-43%, 147+/-43%, and 103+/-42%, respectively). Fibrinogen was significantly higher in diabetic and non-diabetic claudicants compared to controls (4.2+/-1.7, and 3.9+/-1.1, versus 2.9+/-0.5 g/l) and TAT plasma concentration was much higher in diabetic compare to non-diabetic patients and controls (9.8+/-4.4, 1.7+/-1.1, and 1.3+/-0.6 microg, respectively). PF4 concentration was significantly higher in non-diabetic patients with PAOD (34+/-29 UI/ml) when compare to healthy controls (14+/-9 UI/ml), but diabetic PAOD patients with the disease showed lower PF4 concentration (26+/-30 UI/ml). Platelet aggregation with all used activators was similar in all groups likewise hematocrit values, and platelet count. CONCLUSIONS: Complicated DM is linked with significant endothelial perturbation when compared with healthy, but also with PAOD individuals; rheologic parameters are not different from those found in PAOD patients; coagulation system activation but not platelet hyperactivity is associated with DM complicated by PAOD when compared to both control groups.     

Blood levels of total homocysteine in patients with type 1 diabetes (with no complications,diabetic nephropathy and/or retinopathy) and in their non-diabetic relatives

BACKGROUND AND AIM: It has been reported that plasma homocysteine (Hcy) levels in type 1 diabetes (T1DM) patients without renal involvement are higher, similar to or lower than those in healthy controls. METHODS AND RESULTS: We measured plasma Hcy in 60 controls, 79 type 1 diabetics (23 with retinopathy, 22 with nephropathy) and 73 non-diabetic relatives of 30 probands. The female controls had lower levels than their male counterparts: geometric mean 10.5 vs 13.6 mumol/L, p < 0.001. Among the controls, smokers (n = 20) and ex-smokers (n = 12) had higher Hcy levels than non-smokers (n = 28): 13.2 and 13.2 vs 10.9 mumol/L, p < 0.01. Among the diabetics, high plasma Hcy levels were associated with male gender: 11.9 vs 9.1 mumol/L in women, p < 0.01. The patients without complications had higher plasma glucose and hemoglobin A1c (HbA1c) levels (p < 0.001), and lower plasma Hcy (9.2 mumol/L vs 12.2, p < 0.01) and uric acid levels (p < 0.05) than the controls. The patients with nephropathy and higher levels of Hcy (13.0 mumol/L vs 9.0, p < 0.05), and different levels of creatinine (p < 0.01), uric acid (p < 0.01), fibrinogen (p < 0.05), and urinary albumin (p < 0.001) than those with retinopathy. There was no difference in Hcy levels between the patients' relatives and the controls: 11.9 mumol/L in siblings vs 11.6 mumol/L, 13.5 mumol/L in parents vs 12.1 mumol/L. In the control group, plasma Hcy levels were associated with age, gender and smoking; among the diabetics, they correlated with age, gender, smoking, and plasma creatinine and lipoprotein (a) levels. CONCLUSIONS: 1) male gender and smoking are associated with high Hcy levels in healthy people; 2) plasma Hcy levels are lower in T1DM patients than in healthy people (glomerular hyperfiltration and accelerated hepatic transsulfuration?); 3) high Hcy levels are associated with diabetic nephropathy and plasma creatinine levels; and 4) non-diabetic first-degree relatives of type 1 diabetics have normal plasma Hcy concentrations.     

Serum homocysteine levels are increased in women with gestational diabetes mellitus

Serum homocysteine (sHcy) has been found to be elevated in patients with type 2 diabetes mellitus, as well as in other clinical conditions associated with insulin resistance and/or vascular diseases. The aims of this study were to measure the relationship between sHcy with biohumoral markers of insulin resistance in pregnant women affected with gestational diabetes mellitus (GDM). We studied 2 groups of pregnant women categorized, after a 100-g, 3-hour oral glucose tolerance test (OGTT) as nondiabetic (n = 78) or affected with GDM (n = 15), by measuring sHcy, serum folate, albumin, vitamin B(12), uric acid, and lipids. In both groups, peripheral insulin sensitivity was measured by using the OGTT-derived index of Matsuda and DeFronzo (ISI(OGTT)). Serum homocysteine was significantly higher in the group with GDM compared with nondiabetic women (5.88 +/- 2.26 micromol/L v 4.45 +/- 1.52 micromol/L; P =.003); was inversely related to serum folate (r = -.48; P =.0001), and was significantly related to serum albumin (r =.27; P =.009), 2-hour plasma glucose (r =.25; P =.01), as well as to serum uric acid (r =.23; P =.03). No relationship was observed between sHcy and serum vitamin B(12), serum triglycerides, total, or high-density lipoprotein (HDL) cholesterol, mean blood pressure and ISI(OGTT). Vitamin B(12) was correlated with ISI(OGTT) (r =.36; P =.0005) and inversely with mean blood pressure (r = -.24; P =.02). GDM remained significantly associated with higher sHcy concentrations also after adjusting for age, serum folate, albumin, uric acid, ISI(OGTT), and vitamin B(12) (P =.006). In conclusion, we found that sHcy is significantly increased in women with GDM, independently of other confounding variables, is significantly related to 2-hour OGTT plasma glucose, and seems unrelated to insulin resistance in these subjects.