Bioelectrical impedance analysis and diabetes mellitus: which correlation among fructosamine, glycosylated haemoglobin and exchangeable potassium.

AIM: Bioelectrical impedance analysis (BIA) can monitor diabetics suffering from the frequently occurring state of hyperglycemia, as this can cause alterations in the water distribution in the body. The aim of the present study was to evaluate the relationship between the composition of the body and the diabetic disease during decompensation through the impedanciometric analysis in diabetic patients of type 1 and type 2 and to understand the possible alterations of water distribution. METHODS: The study was carried out with 52 subjects (8 males, 44 females), average years 46.5; 15 of them were diabetic, 7 characterised by diabetes of type 1 and 8 by diabetes of type 2. All the patients recruited were in poor metabolic control (glycosylated hemoglobin [HbAlc] >6%). In order to avoid any errors during the evaluation ofa water distribution in the body, patients suffering from hypertension were excluded from the recruitment process. All patients underwent impedanciometry total body using the HUMAN IM SCAN apparatus multifrequency. RESULTS: Through the application of BIA, our work has shown how diabetic patients have a lower quantity of extracellular water (ECW) and exchangeable potassium (Ke) in the body, as compared to non-diabetic patients. The causes of this could be the alteration of the plasmic osmolarity and the possible reduction of the mass of metabolically active cells. Further-more a relationship between fructosamine in the blood and Ke has been found and, alongside another, more significant, between HbA1c and Ke. According to the opinions of the authors, such results are worthy for further studies in order to obtain a greater accuracy in the evaluation of the amount of Ke and an alternative in estimation of metabolic control.

Zinc-dependent low thymic hormone level in type I diabetes.

Zinc is required for optimal functioning of the immune system. It was recently reported that one of the best-known thymic hormones responsible for the maturation and differentiation of the thymus-derived T-lymphocyte line, i.e., serum thymic factor (STF), is biologically active only when bound to zinc ions; in this form it has been called thymulin (Zn-STF). Because low serum and tissue zinc values have been reported to occur in diabetic conditions, and because defects of T-lymphocyte-dependent functions are also present in diabetic patients, even metabolically well-controlled diabetic patients, we investigated the serum level of zinc and the plasma level of both active Zn-STF and inactive STF thymic hormones in 15 young patients suffering from type I (insulin-dependent) diabetes. Serum zinc levels were significantly reduced in diabetic conditions and did not correlate with the degree of metabolic compensation measured by glycosylated hemoglobin. In diabetes, the active form of thymulin is strongly reduced, whereas the inactive form is abnormally elevated. In vitro zinc addition to diabetic plasma samples also induces zinc saturation of inactive thymic hormone molecules: the total thymic hormone measured in these experimental conditions shows values in diabetic patients comparable with those observed in healthy age-matched individuals, suggesting that low thymulin levels recorded in diabetic conditions are due not to a thymic failure in synthesizing and secreting thymic hormone but to a peripheral defect in zinc saturation of the hormone molecules. The zinc-dependent failure of thymic hormone, present even in fairly compensated diabetic conditions, might account for the apparent insulin-independent immunological abnormalities associated with type I diabetes.

Altered cellular Ca2+ and Na+ transport in diabetes mellitus.

Platelet intracellular Ca2+ concentration ([Ca2+]i) and its response to stimuli (ADP and thrombin) were studied in 15 insulin-dependent and 22 non-insulin-dependent diabetes mellitus patients with the fluorescent probe Fura 2. The activity of Ca2(+)-ATPase and Na(+)-K(+)-ATPase, membrane fluidity, and cholesterol and phospholipid content were also determined in platelet membranes. Compared with control subjects, diabetic patients showed 1) increased platelet [Ca2+]i in the resting state, 2) higher Ca2+ levels after stimulation with thrombin and ADP, due entirely to increased resting concentrations, 3) reduced activity of Na(+)-K(+)-ATPase, 4) increased activity of Ca2(+)-ATPase, 5) higher fluidity of the platelet membrane, and 6) increased membrane concentration of total phospholipids. Na(+)-K(+)-ATPase activity was inversely related to platelet [Ca2+]i in each group studied, whereas Ca2(+)-ATPase activity was positively correlated with intracellular Ca2+ levels. The data obtained in diabetic subjects suggest an abnormality in Ca2+ and Na+ transport across the platelet membrane that might be responsible for the reported platelet hyperreactivity to stimuli in diabetes.

Altered platelet membrane dynamic properties in type 1 diabetes.

A modified platelet response to aggregating stimuli is supposed to play a role in the pathogenesis of diabetic macroangiopathy. We studied the fluidity and microheterogeneity of the external surface of the platelet membrane and the activities of the plasma membrane Na+-K+-ATPase and Ca2+-ATPase in 21 men with type 1 diabetes and in 20 control subjects before and after in vitro thrombin addition. In the resting state, platelets from type 1 diabetic patients showed an increased fluidity and microheterogeneity of the platelet membrane, a higher Ca2+-ATPase activity, and a reduced Na+-K+-ATPase activity in comparison with platelets from healthy subjects. The fatty acid composition was also modified, with increased C 16:1 and decreased C 18:0 content. Control cells incubated with thrombin showed a modification of the membrane parameters opposite to the response observed in type 1 cells after the stimulation. The incubation of control platelets in the resting state with high concentrations of glucose modified the fluidity of the plasma membrane Na+-K+-ATPase and Ca2+-ATPase activities in an opposite way in comparison with the alterations observed in type 1 platelets. This study suggests that in type 1 diabetic patients, the platelet membrane responds to activation with a molecular remodeling different from the response of healthy subjects. The abnormal organization of the membrane might contribute to the altered platelet functions in type 1 diabetic patients, but acute exposure to high glucose levels does not seem able to modify the platelet membrane in the way observed in type 1 diabetes.

Reduced Na(+)-K(+)-ATPase activity and plasma lysophosphatidylcholine concentrations in diabetic patients.

A fraction from normal human plasma inhibiting Na(+)-K(+)-ATPase has been recently identified as lysophosphatidylcholine (LPC). The aim of this study was to investigate the existence of a relationship between the activity of the cellular membrane Na(+)-K(+)-ATPase and plasma LPC in human diabetes. We studied 10 patients with insulin-dependent-diabetes mellitus (IDDM), 14 patients with non-insulin-dependent diabetes mellitus (NIDDM), and 10 sex- and age-matched control subjects. Plasma LPC concentrations were increased in both IDDM and NIDDM patients compared with control subjects. Na(+)-K(+)-ATPase activity was reduced in both groups of patients in erythrocyte and platelet membranes. There was a significant correlation between the concentrations of plasma LPC and Na(+)-K(+)-ATPase activity in both erythrocyte and platelet membranes (P < 0.01). To investigate the effect of LPC on the enzyme, Na(+)-K(+)-ATPase activity was determined in erythrocyte membranes obtained from six healthy subjects after in vitro incubation with increasing concentrations of LPC (1-10 microM). Enzymatic activity was significantly reduced by in vitro LPC at a concentration of 2.5 microM, with a further decrease at 5 microM. These data suggest that the decrease in Na(+)-K(+)-ATPase activity in diabetes might be due to increased LPC concentrations.

Renal disease as a determinant of increased lipoprotein(a) concentrations in diabetic patients.

OBJECTIVE: This study examined the hypothesis that kidney function is an independent determinant of lipoprotein(a) [Lp(a)] concentrations in people with diabetes. RESEARCH DESIGN AND METHODS: Lp(a) concentrations were measured in plasma samples from 273 type 2 and 223 type 1 diabetic patients recruited from a diabetes clinic. Kidney function was categorized as normal or pathological according to plasma creatinine levels and creatinine clearance rates. RESULTS: Macroalbuminuria was uniformly associated with significantly raised plasma concentrations of Lp(a) regardless of the marker used to identify kidney dysfunction. In contrast, in patients with microalbuminuria, significantly raised plasma Lp(a) levels were observed only when creatinine clearance rates or plasma creatinine levels indicated pathological kidney function. These conclusions were independent of diabetes type. CONCLUSIONS: In microalbuminuria and apparently in normoalbuminuria, altered kidney function determined by creatinine clearance rates or creatinine levels appears to be a major determinant of raised Lp(a) levels in both type 1 and type 2 diabetic patients. In contrast, Lp(a) concentrations were uniformly raised in patients with macroalbuminuria.

Apolipoprotein E polymorphism as a risk factor for vascular disease in diabetic patients.

OBJECTIVE: To examine the prevalence of cardiovascular disease in diabetic patients as a function of apolipoprotein (apo) E polymorphism. RESEARCH DESIGN AND METHODS: The apo E phenotypes and plasma lipid, lipoprotein, and apo levels were determined for 517 Italian diabetic patients. The prevalence of cardiovascular disease (defined as ischemic heart disease [HD] and/or peripheral vascular disease and/or cerebrovascular disease) was assessed as a function of apo E polymorphism at entry and after 4 years. RESULTS: The occurrence of vascular disease did not differ significantly between diabetic patients in the various categories of apo E phenotype either at entry into the study or after 4 years. When expressed as a percentage of patients with disease, we observed--for E2, E3, and E4 carriers, respectively--at entry: IHD, 20.0% (n = 14), 21.0% (n = 79), and 21.5% (n = 14); and macroangiopathy, 24.3% (n = 17), 29.3% (n = 110), and 24.6% (n = 16). Apo E polymorphism did not make a significant contribution to multiple logistic regression models designed to identify the factors associated with the occurrence of vascular disease in diabetic patients. CONCLUSION: Apo E polymorphism and, notably, the apo E4 allele cannot be universally considered as a particular risk factor for cardiovascular disease in diabetic patients.

Abnormal membrane fluidity and acetylcholinesterase activity in erythrocytes from insulin-dependent diabetic patients.

An alteration in the enzymatic properties of the erythrocyte membrane acetylcholinesterase (AchE) and Na+,K+-ATPase has been described in experimental diabetes mellitus. We studied erythrocyte membrane fluidity and AchE and Na+,K+-ATPase activities in 15 insulin-dependent diabetic patients and 11 normal subjects. Fluidity was assessed by fluorescence polarization, using 1,6-diphenyl-1,3,5-hexatriene as a probe, and AchE and Na+,K+-ATPase activities were measured enzymatically. We found a significant increase in the enzymatic activity of AchE and a change in its enzymatic properties in diabetic patients compared with those in normal subjects. AchE activity correlated inversely with membrane fluorescence polarization, which was decreased in the diabetic patients, indicating an increase in membrane fluidity. Na+,K+-ATPase activity was reduced in the diabetic patients and correlated positively with the fluorescence polarization values. We hypothesize that the abnormal dynamic properties of the erythrocyte membrane may play a major role in determining the described change in enzymatic activity.

Modifications induced by plasma from insulin-dependent diabetic patients and by lysophosphatidylcholine on human Na+,K(+)-adenosine triphosphatase.

To investigate the molecular mechanisms of the inhibition of Na+,K(+)-adenosine triphosphatase (Na+,K(+)-ATPase) in diabetes mellitus, we incubated Na+,K(+)-ATPase purified from human placenta of six healthy nondiabetic women with plasma from six insulin-dependent diabetic (IDDM) men and six healthy controls and with different concentrations of lysophosphatidylcholine (LPC). We determined the enzyme activity, anthroyl ouabain-binding capacity, dissociation constant (Kd), and average lifetime values (tau) by the static and dynamic fluorescence of anthroyl ouabain. The lipid annulus of the enzyme was studied by static and dynamic fluorescence of 1-(4-trimethylamino-phenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH). Moreover, we studied the lipid microenvironment surrounding the Na+,K(+)-ATPase purified from the placentas of six healthy women and six insulin-dependent diabetic women, determining the percent composition of phospholipids of the lipid annulus. The addition of total and protein-free IDDM plasma to normal Na+,K(+)-ATPase significantly inhibited the enzymatic activity even at the lowest concentration studied (1: 100), whereas the ouabain-binding capacity, Kd, and tau were not affected by IDDM plasma. The fluorescence polarization and lifetime values of TMA-DPH were significantly decreased by diabetic plasma. The incubation of Na+,K(+)-ATPase with LPC caused an inhibition of the enzymatic activity without modifications of the anthroyl ouabain-binding capacity and dissociation constant. The fluorescence polarization and lifetime values of TMA-DPH were significantly decreased by 5 mumol/L LPC. The study of the phospholipids surrounding Na+,K(+)-ATPase demonstrated a significant increase in the percent LPC content in IDDM patients compared with controls together with a concomitant decrease in phosphatidylcholine. These observations indicate that the inhibition caused by diabetic plasma on Na+,K(+)-ATPase is not dependent on a modification of the ouabain-binding site and that it seems to mimic the effect of LPC addition. A link between modification of the lipid moiety of the enzyme and Na+,K(+)-ATPase inhibition might be hypothesized.

Influence of low density lipoprotein from insulin-dependent diabetic patients on platelet functions.

In the present work we studied in vitro the action of low density lipoproteins (LDL) isolated from normolipemic insulin-dependent diabetic (IDDM) patients on transmembrane cation transport, nitric oxide synthase (NOS) activity, and aggregating response to stimuli of platelets from healthy subjects to elucidate whether the modified interaction between circulating lipoproteins and cells might be one of the pathogenetic mechanisms of the increased platelet activation in IDDM. LDL were obtained by discontinuous gradient ultracentrifugation from 15 IDDM out-patients and 15 sex- and age-matched healthy subjects and used for incubation experiments with control platelets. Lipid composition and hydroperoxide concentrations were studied in LDL. Platelet aggregation responses to ADP, NOS activity, cytosolic Ca2+ concentrations, and platelet membrane Na+/K+-adenosine triphosphatase (Na+/K+-ATPase) and Ca2+-ATPase activities were measured after incubation. IDDM LDL showed an increased lysophosphatidylcholine content compared with that of control LDL. IDDM LDL significantly increased the platelet aggregating response to ADP, cytosolic Ca2+ concentrations, and plasma membrane Ca2+-ATPase activity and significantly reduced NOS activity and platelet membrane Na+/K+-ATPase activity compared with those of platelets incubated in buffer or cells incubated with control LDL. The effects exerted by IDDM LDL on platelet suspensions from healthy subjects mimic the alterations observed in platelets from diabetic subjects in basal conditions. Both the decreased activity of NOS and the higher cytoplasmic concentrations of Ca2+ might cause increased platelet activation, as observed in IDDM. In conclusion, the present study suggests a new mechanism with a potential role in the early development of atherosclerosis in diabetic patients, i.e. an altered interaction between circulating lipoproteins and platelets.

One- and two-compartment minimal models detect similar alterations of glucose metabolism indexes in hypertension.

A standard intravenous glucose tolerance test (IVGTT) was performed in 10 nondiabetic patients with essential hypertension (H group) and 9 normotensive control subjects (N group). A 2-compartment minimal model (2CMM) of glucose kinetics was applied to estimate indexes of glucose effectiveness, S2G and insulin sensitivity, S2I, by means of a maximum a posteriori (MAP) bayesian estimation technique. These estimates were contrasted to the S1G and S1I indexes provided by the classic minimal model (1CMM). In both the N group and the H group, the 2CMM underestimated the glucose effectiveness and overestimated the insulin sensitivity. In the H group, S2G was, on average, 63% of S1G (P > .05) and S2I was 137% of S1I (P > .05). In the N group S2G was 67% of S1G (P > .05) and S2I was 134% of S1I (P > .05). The 2CMM detected a reduction of approximately 40% (P > .05) and approximately 48% (P > .05) in S2G and S2I estimates, respectively, from the N group to the H group. Despite its reduced complexity, the 1CMM also detected a reduction of approximately 35% (P < .05) and approximately 49% (P < .05) in the S1G and in S1I indexes, respectively. Thus, the 1CMM and 2CMM showed a substantial equivalence in detecting a severe reduction in insulin sensitivity and impaired glucose effectiveness in hypertensive patients compared with normal.

Increased susceptibility to lipid oxidation of low-density lipoproteins and erythrocyte membranes from diabetic patients.

The aim of the present study was to determine if low-density lipoproteins (LDLs) and red blood cell (RBC) membranes from diabetic patients present an increased susceptibility to lipoperoxidation, which might be related to the increased incidence of atherosclerosis in diabetes. LDLs and RBC membranes were isolated from 11 insulin-dependent (IDDM) and 18 non-insulin-dependent diabetic (NIDDM) patients and exposed to a peroxidative stress by incubation with phenylhydrazine. The susceptibility to peroxidation was determined by measuring the production of thiobarbituric acid-reactive substances (TBARS) after the incubation. The following parameters were also evaluated: plasma glucose, triglycerides (TG), phospholipids (PL), total and high-density lipoprotein (HDL) cholesterol, apolipoprotein (apo) A-I, apo B, hemoglobin A1c (HbA1c), LDL PL and cholesterol, LDL fatty acid composition, and RBC membrane PL and cholesterol. Although they were apparently normolipidemic, diabetic patients showed an increased susceptibility to peroxidation in LDLs and erythrocyte membranes as compared with control subjects. The amount of arachidonic acid in LDLs and the PL concentration of RBC membranes from diabetic patients were significantly higher than in normal subjects. The increased lipoperoxidability of both RBC membranes and LDLs might play a central role in the pathogenesis of the vascular complications of diabetes mellitus.

Modified fluidity and lipid composition in lipoproteins and platelet membranes from diabetic patients.

The interaction between lipoproteins and the platelet membrane has been proved to cause a modification in cellular functions. We studied 12 men with insulin-dependent diabetes mellitus (IDDM), 14 men with noninsulin-dependent diabetes mellitus (NIDDM), and 26 age-matched healthy men on the same diet. We determined fluidity by measuring the fluorescence polarization (P) of the probe 1,6-diphenyl-1,3,5-hexatriene (DPH) both in platelet membranes and in lipoproteins isolated by ultracentrifugation in NaBr density gradient. The lipid composition of lipoproteins and of platelet membranes was determined by enzymatic methods. The fluidity of platelet membranes was significantly increased both in patients affected by NIDDM and in subjects with IDDM compared with normal subjects. Low-density lipoproteins (LDL) showed an increased fluidity only in NIDDM patients. A percent increase in the triglyceride content was observed in all lipoprotein fractions in diabetic subjects. Increased phospholipid content was found in the platelet membranes from IDDM and NIDDM patients. The change in LDL fluidity observed in NIDDM patients might determine altered interactions between the lipoprotein and cellular receptors. The role of lipoproteins in the modulation of the platelet membrane properties in diabetes mellitus deserves further studies.

Osteopenia associated with non-insulin-dependent diabetes mellitus: what are the causes?

This study investigated whether alterations in bone mineral content (BMC) and/or in the phosphate-calcium metabolism exist in non-insulin-dependent diabetes mellitus (NIDDM); whether they are linked to glycaemic control and whether antidiabetic therapy--oral agents or insulin--influences BMC and mineral metabolism. A cross-section assessment compared BMC and mineral metabolism in 60 well-controlled and 50 poorly controlled diabetic patients under oral hypoglycaemic therapy with 50 healthy controls. A longitudinal assessment improved the high glucose levels of the poorly controlled diabetic group either by increasing oral treatment or by adding a bedtime NPH insulin. Glycaemic control, BMC and mineral metabolism were followed-up for 1 year. In NIDDM patients BMC is reduced. This reduction is more marked in poorly controlled diabetic patients. In well-controlled diabetes osteocalcin levels are low. In poorly controlled patients glycosuria, hypercalcuria and parathyroid hyperactivity are present. In both groups vitamins 25(OH)-D, 1,25(OH)2-D and calcitonin levels are normal. Improving metabolic control increased BMC, normalized urinary calcium excretion and parathyroid activity and reduced osteocalcin levels. The type of anti-diabetic therapy does not have any significant effect upon BMC or upon phosphate-calcium metabolism. In conclusion, in NIDDM a hard-to-define osteoblast deficit appears to exist. In poorly controlled diabetes the loss of BMC is aggravated by the negative calcium balance caused by the renal calcium leak. This is due to glucosuric-induced osmotic diuresis and is maintained by parathyroid activation.

Diagnosis of MODY in the offspring of parents with insulin-dependent and non-insulin-dependent diabetes mellitus.

Maturity Onset Diabetes of the Young (MODY) is an autosomal dominant monogenic form of type 2 diabetes mellitus (DM) representing 5% of youth-onset DM in the Caucasian population. In young adults the disease can be present as either non-insulin dependent or insulin-dependent DM. The diagnosis of this genetic disorder in children and adolescents is rare because of the mild glucose metabolism disorder at this time. We performed a metabolic, autoimmune and genetic study in 40 offspring of young parents affected by insulin-dependent DM (Group A) and in 35 offspring of young parents affected by early-onset non-insulin-dependent DM (Group B). Two children of Group A (5%) were found to be affected by fasting hyperglycemia and carry a GCK gene mutation that in one case was present also in the diabetic father. Eighteen offspring of Group B (51%) were positive for GCK or HNF-1alpha gene mutations present in the affected parents. All but two of these young patients had impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Eleven of them were younger than 16 years. We conclude that screening for DM in youth should be extended to MODY in young families with both non-insulin-dependent and insulin-dependent DM. The sensitivity of the metabolic tests will precede the genetic diagnosis.

Age-related macular disease in diabetes mellitus.

Age-related macular degeneration (ARMD) is one of the leading causes of vision impairment in the elderly and its frequency in general population increases with aging. The etiology of this disease has remained so far unknown. The relationship between ARMD and diabetes mellitus was studied in the present work. Fundus oculi was investigated in 292 diabetic patients older than 50 years and with more than 14 years of duration of diabetes (time since diagnosis). A group of 375 non diabetic, non hypertensive subjects matched for age was studied as control. ARMD frequency was significantly higher in diabetics compared to controls (p < 0.005); and also in type II diabetics (non-insulin dependent diabetes mellitus = NIDDM) compared to type I (insulin dependent diabetes mellitus = IDDM) (p < 0.001). Older diabetic patients showed an increased frequency of ARMD while no correlation with the duration of the disease emerged. Macular damage was not linked to microangiopathy (retinopathy), hypertension or gender; on the contrary, it appeared to be associated with dyslipidemia. On the basis of these data one can conclude that diabetes mellitus can exert an unfavorable effect on macular age-related phenomena even if the pathogenetic mechanism is at present obscure.

Diabetes mellitus and chronic heart failure.

Cardiovascular disease has a high prevalence in diabetic patients. Diabetes mellitus is an important risk factor for atherosclerosis and coronary disease mainly through obesity, hyperlipidemia, insulin-resistance, hyperinsulinemia, hyperglycemia and altered homeostasis. The correlation between diabetes and chronic heart failure is not widely documented in the literature. According to the Framingham study, the incidence of cardiovascular morbidity per year is 39.1% in diabetic males and 17.2% in diabetic females; chronic heart failure afflicts 7.6% of diabetic males and 11.4% of diabetic females. Actual knowledge about pathophysiology suggests that cardiac involvement in diabetes is not only related to macrovascular injury but also to other factors, such as alterations of autonomic nervous system, that can contribute to diabetic cardiopathy. The present study evaluated the prevalence of chronic heart failure in an Italian diabetic population in order to discuss the rationale of the therapeutic strategies.

Coronary heart disease, type 2 diabetes mellitus and cardiovascular disease risk factors: a study on a middle-aged and elderly population.

The risk for all the manifestations of atherosclerotic disease is increased in patients affected by type 2 diabetes mellitus. The aim of the present work was to evaluate the prevalence of coronary heart disease (CHD) in a well-characterized middle-aged and elderly Italian diabetic population. The population studied included 3862 subjects, i.e. all the patients affected by type 2 diabetes of age >or=50 years attending the outpatient diabetes care unit of INRCA in Ancona (Italy) from 1 August 1997 to 31 July 1998. We collected and analysed both clinical and laboratory data by means of a computerized data base for the outpatient clinic management. The prevalence rate of CHD was 20.25% in this population. The groups with CHD and without CHD did not differ significantly with respect to age at onset of diabetes, body mass index and HbA1c levels, while patients with CHD were significantly older than patients without CHD and had a longer duration of diabetes. The prevalence of patients with hypertension (52.9 vs 63.0%, P<0.001), hypercholesterolemia (11.6 vs 14.1%, P<0.05) and hyperlipidemia (17.8 vs 23.3%, P<0.001) was significantly higher in the group of diabetic subjects affected by CHD than in patients not affected by heart ischemic disease. It might be hypothesized that the improvement of metabolic profile and the currently feasible control of non-diabetic risk factors could reduce cardiovascular disease rates in type 2 diabetic patients.

Influence of body mass on glycemic control in a type 2 diabetic population: a 3-year follow-up.

Obesity is often associated with type 2 (non insulin-dependent) diabetes. A growing body of evidence support the hypothesis that these two diseases share a common pathogenesis. Nevertheless, experience derived from clinical observation on type 2 diabetic patients indicates that reduction of body weight is not always accompanied by an improvement in metabolic control and that a good metabolic control is often obtained without influencing body composition. Aim of the present study was to evaluate the relationship between body mass and glycemic control in a type 2 diabetic population by a 3 years observational study. A cohort of 562 subjects was studied. At entry more than 80% of patients were overweight or obese according to the body mass index (BMI) scale and this proportion was not significantly reduced at the end of the follow-up. At entry all patients had a glycosylated hemoglobin (HbA1c) value above 8.1% whereas at the end of follow-up more than 2/3 of patients were in good metabolic control. No relationship was observed between modification of body mass and metabolic control. These data confirm the high frequency of obesity among type 2 diabetic individuals but they suggest that impaired glucose metabolism and alteration of body weight have different pathogenesis.

Morphological alterations and increased resistance to hemolysis in t-butyl hydroperoxide incubated RBC from elderly subjects.

The response of human red blood cells (RBC) to oxidative stress has been studied with the aim to evaluate any difference in the behavior of cells from young and old subjects. Thus, RBC from 5 young (27 +/- 2 years) and 5 old (80 +/- 5 years) individuals have been treated with the organic peroxide t-butyl hydroperoxide (TBHP). The two groups behaved differently: after 4 hrs of incubation in 0.5 mM TBHP, RBC from young donors showed a higher level of hemolysis; instead, RBC from old individuals showed abnormal morphologies, being absent in unstressed RBC, with constriction and budding, which could be identified as poikilocytosis. The same abnormal forms are found in patients with spectrin mutation, leading us to hypothesize that TBHP causes damage to the cytoskeletal spectrin. This suggests that poikilocytosis might be an early stage of red blood cell hemolysis because their presence is associated to a lower level of hemolysis.