Insulin-treated Non-insulin-dependent Diabetes Mellitus Research Articles

Inefficiency of insulin therapy to correct apolipoprotein A-I metabolic abnormalities in non-insulin-dependent diabetes mellitus

Non-insulin-dependent diabetes mellitus (NIDDM) is associated with low high density lipoprotein (HDL) cholesterol and apoA-I, related to an increased apoA-I fractional catabolic rate. This stable isotope kinetic experiment, using l-[1- 13C] leucine, was designed to study the effect of insulin therapy on HDL apoA-I and A-II metabolism in poorly controlled NIDDM patients. A kinetic study was performed in five control subjects and in six NIDDM patients before and two months after the introduction of insulin therapy. ApoA-I and A-II were modelled using a monoexponential function. Insulin treatment was able to correct neither the low HDL apoA-I concentration observed in NIDDM patients (1.14±0.19 vs. 1.16±0.12 g l −1 (controls: 1.33±0.14)), nor the HDL apoA-I hypercatabolism (0.39±0.11 vs. 0.34±0.05 pool d −1, (controls: 0.23±0.01, P< 0.01)). HDL apoA-I production rate was increased in NIDDM patients compared to control subjects and was not modified by insulin (0.45±0.12 vs. 0.39±0.08 g d −1 l −1, (controls: 0.31±0.04, P< 0.05)). HDL apoA-II kinetic parameters were initially not significantly different between NIDDM patients and control subjects, and were not modified by insulin. The decreased insulin sensitivity, assessed by the insulin suppressive test, was not modified by insulin therapy in NIDDM patients. HDL apoA-I fractional catabolic rate was significantly correlated to HDL triglyceride/cholesteryl ester and triglyceride/protein ratios, which were significantly higher in NIDDM patients than in controls and were not modified by insulin therapy. The persistence of insulin resistance and of high neutral lipid exchanges between triglyceride rich lipoproteins and HDL in insulin-treated NIDDM patients probably explain the inefficiency of insulin therapy to correct HDL apoA-I metabolic abnormalities.

Diabetic peripheral neuropathy: Effects of age, duration of diabetes, glycemic control, and vascular factors

The aim of this study was to determine the factors associated with diabetic peripheral neuropathy and more particularly its relation to precisely assessed microangiopathy. Peripheral neuropathy was assessed in 135 diabetic patients: 28 insulin-dependent diabetes mellitus (IDDM), 85 non-insulin-dependent diabetes mellitus (NIDDM), and 22 insulin-treated NIDDM patients, on the basis of both clinical findings and extensive electrophysiological testing (four motor nerves and four sensory nerves, and right and left Hoffmann's reflex), using a total of 20 parameters. The percentage of women with severe clinical neuropathy was significantly higher than that of men, and the clinical neurological stage correlated significantly with age and duration of diabetes. According to multivariate analysis the clinical stage correlated only with gender and duration of diabetes. Several electrophysiological parameters were significantly more abnormal in women and correlated with age, type and duration of diabetes, and recent glycemic control. The multivariate analysis showed that 17 electrophysiological parameters correlated with duration of diabetes, nine correlated with age, seven with glycemic control, and only one with gender. The presence of clinical neuropathy also correlated with presence of retinopathy, arterial hypertension, macroangiopathy, and biological signs of nephropathy. All the electrophysiological parameters were significantly more abnormal in patients with retinopathy or macroangiopathy than in patients without these complications. Separate parameter analysis showed that at least one abnormal electrophysiological parameter was almost always found in patients with retinopathy, macroangiopathy, or incipient nephropathy, but abnormalities were also found to a slightly lesser extent in patients without these complications. Multivariate analysis showed that when duration of diabetes, retinopathy, macroangiopathy, and biological signs of nephropathy were introduced into the model, 11 electrophysiological parameters correlated with duration of diabetes, 11 with retinopathy, seven with macroangiopathy, and five with a sign of nephropathy. This study demonstrates that age and glycemic control have an effect, and diabetes duration a major effect on peripheral nerve function. It suggests that vascular factors may participate in the development of nerve lesions.

Diabetes teaching—outcome analysis

A comprehensive database has been maintained on patients attending the St. Paul's Hospital Diabetes Teaching and Treatment Centre (DTTC) since 1984. In November 1995, four sets of patients, all of whom had returned to the Centre, were identified for an outcome study. The sets were: insulin-dependent diabetes mellitus (IDDM), diet-treated non-insulin-dependent diabetes mellitus (NIDDM), oral agent-treated NIDDM, insulin-treated NIDDM. Data on glycosylated hemoglobin (A1c) values, percent ideal body weight (%IBW), home blood glucose monitoring (HBGM)/week were analysed for all sets; data on hypoglycemic events/month were analysed only for the group with IDDM. Results demonstrated that patients in all groups performed significantly more HBGM over time. Downward change in %IBW in the diet-treated and oral agent groups was significant. Upward change in %IBW was significant in the IDDM group. Hypoglycemic events did not significantly increase in IDDM patients even though A1c improved. Most notably, the A1c values improved in all four groups up to 8 years after the first DTTC visit. Implications for practice are suggested.

Health care for persons with non-insulin-dependent diabetes mellitus. The German experience.

A structured treatment and education program for patients with non-insulin-dependent diabetes mellitus (NIDDM) who are not taking insulin was developed, evaluated, and implemented at the primary health care level throughout Germany. The program is based on the definition of individual and pragmatic therapeutic goals for each patient, primarily using nondrug treatment, which includes systematic glycosuria self-monitoring by the patients and four structured sessions of group education held in a general practitioner's office. After documentation of the program's efficacy in a randomized, controlled trial and several pilot projects, the program has been officially incorporated into the general German health care scheme and includes payment to practicing physicians for each patient treated. More than 12,500 primary health care physicians have participated in special 2-day postgraduate courses given by diabetologists; these courses are a precondition to participating in the program. As part of the primary health care scheme, the NIDDM program will be continuously monitored for quality control and efficiency. Currently, similar structured treatment and education programs targeted to primary health care physicians are being introduced for both insulin-treated NIDDM and arterial hypertension.

Evaluation of cardiac sympathetic nervous function by 123I-metaiodobenzylguanidine scintigraphy in insulin-treated non-insulin dependent diabetics with hypoglycemia unawareness.

The association between the lack of adrenergic symptoms during hypoglycemia and myocardial 123I-metaiodobenzylguanidine (MIBG) accumulation was investigated in 12 insulin-treated non-insulin-dependent diabetes mellitus (NIDDM) patients who had no evidence of heart disease. These patients were divided into 2 groups according to the presence (group A) or absence (group B) of adrenergic symptoms during hypoglycemia. Autonomic function tests revealed significantly severe autonomic dysfunction in group B compared to that in group A. Insulin infusion test indicated no significant difference in the catecholamine response between the two groups. 123I-MIBG scintigraphy showed that the heart/mediastinum ratio of MIBG uptake was significantly lower, and scintigraphic defect was greater in group B than in group A. There were no significant differences in the washout rate between the two groups. These results suggested that the lack of adrenergic symptoms during hypoglycemia may be associated with cardiac sympathetic nervous dysfunction in insulin-treated NIDDM patients, and this dysfunction is mainly due to cardiac sympathetic denervation.

Frequency and Determinants of Diabetes Patient Education Among Adults in the U.S.Population

To determine the proportion of adults with diabetes in the U.S. who have received diabetes patient education and to assess factors that determine whether patients receive this education. A questionnaire on diabetes was administered to a representative sample of 2,405 diabetic individuals > or = 18 years of age in the U.S. population. The questionnaire inquired about whether these individuals had ever attended a diabetes education class or program. Sociodemographic and clinical factors that may influence participation in patient education were also determined. Of all people with diabetes, 35.1% had attended a class or program about diabetes at some time during the course of their disease, including 58.6% of individuals with insulin-dependent diabetes mellitus, 48.9% of insulin-treated individuals with non-insulin-dependent diabetes mellitus (NIDDM), and 23.7% of NIDDM individuals not treated with insulin. Younger age, black race, residence in the midwest region of the U.S., higher level of education, and presence of diabetes complications were consistently associated with having had diabetes education for people with NIDDM. Although increasing income was associated with patient education for NIDDM individuals not treated with insulin, it was not an independent determinant for insulin-treated NIDDM individuals. NIDDM individuals not treated with insulin who lived alone were more likely to have had patient education than those who did not live alone. Not having a diabetes physician or not visiting one in the past year was associated with a higher likelihood of patient education for non-insulin-treated NIDDM individuals. A large proportion of patients with diabetes has never received diabetes education. Patient education has been recognized for its contributions to reducing the morbidity and mortality of diabetes. Consequently, special attention should be directed to the subgroups of individuals, such as those not taking insulin, those with lower socioeconomic status, and those living outside urban areas, in which the frequency of diabetes patient education is particularly low.

Rationale for the association of sulfonylurea and insulin

Approximately 20–30% of patients with non-insulin-dependent diabetes mellitus (NIDDM) started on sulfonylureas fail to respond to treatment (primary failure); in the remaining patients, secondary failure to sulfonylurea therapy occurs at a rate of 5–10% per year. On the other hand, in insulin-treated NIDDM patients a progressive increase in insulin requirement can occur without significant improvement in glucose control. In these patients the combination of oral agents with insulin therapy may be useful. The rationale behind this therapeutic approach resides in the synergistic action of the two agents on specific mechanisms responsible for glucose intolerance and hyperglycemia. Long-acting insulin, administered as a single dose at supper or bedtime, should restrain excessive overnight hepatic glucose production, thus allowing a significant reduction in fasting glucose concentrations. A lower ambient glucose level should favor the stimulatory effect of sulfonylureas on insulin secretion. Sulfonylurea treatment should increase the portal inflow of secreted insulin with a resultant increase in insulin levels draining into liver, thus reducing postprandial hepatic glucose output. Moreover, sulfonylureas might improve insulin action on its target tissue (i.e., muscle), thus increasing overall insulin-mediated glucose metabolism. The reduction in prevailing plasma glucose levels will reduce the toxic effect of hyperglycemia on the β-cell and on insulin-sensitive tissues. On this basis, NIDDM patients with secondary failure of monotherapy may benefit from combined therapy. Nevertheless, the effects of combined therapy should be strictly monitored and intensive insulin therapy promptly started if poor control persists.

Effects of glyburide on In Vivo insulin-mediated glucose disposal

The purpose of this study was to examine the effects of glyburide on peripheral (muscle) and hepatic insulin sensitivity in patients with non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM) as well as in healthy control subjects. In protocol 1, 10 patients with NIDDM and seven young healthy control subjects were studied. Changes in insulin sensitivity (40 frsol| mU/ m 2 · min euglycemic insulin clamp), hepatic glucose production (3-[ 3H]glucose turnover), and insulin secretion (+125 mg/dL) hyperglycemic clamp) were measured before and after 3 months (in patients with NIDDM) and 6 weeks (in young control subjects) of glyburide therapy. In protocol 2, five patients with IDDM and eight patients with insulin-treated NIDDM were evaluted before and after two months of glyburide therapy (20 mg per day). Changes in daily insulin requirements, 24-hour plasma glucose profiles, glycohemoglobin, glucagon-stimulated C-peptide secretion, insulin sensitivity, and hepatic glucose production were measured. In protocol 1, glyburide significantly improved insulin sensitivity (p <0.01) and insulin secretion (p <0.01) in the NIDDM patients. The elevated rates of hepatic glucose production (2.4 ± 0.3 mg/kg · min) were reduced after glyburide therapy (1.7 ± 0.2 mg/kg · min; p <0.01) and were highly correlated with an improvement in fasted plasma glucose levels (r = 0.92; p <0.001). Insulin sensitivity also improved in the young healthy control subjects after glyburide therapy (6.5 ± 0.5 to 7.6 ± 0.7 mg/kg · min; p <0.05). In protocol 2, glyburide treatment produced no changed in daily insulin requirement (54 ± 8 versus 53 ± 7 units per day), mean 24-hour glucose levels (177 ± 20 versus 174 ± 29 mg/dL), glycohemoglobin (10.1 ± 1.0 percent versus 9.5 ± 7 percent), C-peptide secretion, insulin sensitivity, or basal hepatic glucose production (p values not significant) in the IDDM patients. In contrast, the insulin-treated NIDDM patients had siginificant reductions in mean daily insulin requirement (72 ± 6 versus 58 ± 9 units per day; p = 0.05), mean 24-hour plasma glucose levels (153 ± 10 to 131 ± 5 mg/dL; p <0.05), and glycohemoglobin levels (10.3 ± 0.7 percent to 8.0 ± 0.4 percent; p 0.05) and an improvement in C-peptide secretion (0.24 ± 0.07 to 0.44 ± 0.09 pmol/mL; p = 0.08). Stimulated C-peptide levels were highly correlated with a reduction in insulin dose observed during the 2-month treatment period (r = 0.93; p <0.001). Insulin sensitivity improved slightly but not significantly after glyburide treatment. It is concluded that glyburide improves glycemic control by a combination of mechanisms, including: (1) enhancement of peripheral (muscle) insulin sensitivity; (2) reduction in basal hepatic glucose production; and (3) potentiation of glucose-stimulated insulin secretion. Because no benefit is observed in IDDM patients, it appears that shome endogenous insulin secretory capacity is required for these effects to become evident.

Diurnal Variation of Blood Ketone Bodies in Insulin-Dependent Diabetes mellitus and Noninsulin-Dependent Diabetes mellitus Patients: The Relationship to Serum C-Peptide Immunoreactivity and Free Insulin

We examined whether the rise in ketone body concentration around midnight and in the early morning was due to the lack of free insulin (IRI) or excess of insulin counterregulatory hormones such as human growth hormone (hGH), cortisol and glucagon in noninsulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM) patients and whether the monitoring of blood ketone body concentration was clinically useful as an index of metabolic control for deciding to increase or decrease the insulin dose in the treatment of diabetes mellitus. Serum levels of 3-hydroxybutyrate (3-OHBA), acetoacetate (AcAc) and 3-OHBA/AcAc ratio before breakfast were significantly increased in insulin-treated NIDDM patients with well-controlled fasting plasma glucose levels and IDDM patients compared to those in normal subjects. Mirror image diurnal changes were found between serum concentrations of 3-OHBA and serum C-peptide or free IRI in normal subjects and NIDDM patients treated with diet alone or sulfonylurea during the 24-hour daily profiles. However, there were no correlations between 3-OHBA and free IRI in the NIDDM patients treated with insulin and IDDM patients who had a much larger increase in the mean concentration of serum 3-OHBA at 6 a.m. caused by a low concentration of free IRI. Counterregulatory hormones were not increased in IDDM patients compared to normal subjects in the early morning. Cortisol/free IRI and hGH/free IRI molar ratios were significantly increased in NIDDM and IDDM patients compared to normal subjects in the early morning, but glucagon/free IRI molar ratio was not changed between IDDM and normal subjects. In conclusion, the early morning rising of ketone body concentration in insulin-treated diabetic patients, particularly IDDM patients, is due to the absolute lack of free IRI and/or the relative lack of free IRI to the levels of hGH or cortisol, and the monitoring of 3-OHBA is clinically useful as a more sensitive index of metabolic control.