Insulin pump therapy in patients with type 1 diabetes

Both Continuous Subcutaneous Insulin Infusion (CSII) and Multiple Daily Injections (MDI) are effective ways of implementing intensive management of DM1 to attain near normal glycemic levels and a more flexible lifestyle. CSII is as safe as MDI and has some advantages over it mostly in diabetic patients with frequent hypoglycemias with important dawn phenomenum, gastroparesia, during pregnancy, in children and in patients with an erratic way of living. CSII allows a better chance to reach better glycemic control with less hypoglycemia, asymptomatic hypoglycemias and a better quality of life. Besides, risks are lower and adverse events are less frequent in DM1 patients under CSII as compared to MDI. To obtain results like this, a careful adjustment of basal and boluses insulin doses and an adequate patient follow-up are essential.     

Insulin therapy in elderly patients with diabetes mellitus

Insulin therapy is an effective measure of improving glucose control even in elderly patients with type 2 diabetes. However, it is controversial whether insulin therapy does disturb the quality of life (QOL) as well as cognitive function in the elderly. In our previous study of 455 diabetic patients, the well-being as assessed by the morale scale was similar in three treatment groups. In contrast, the symptom-burden, social burden, and worry about diabetes as assessed by the Elderly Diabetes Burden Scales was more increased in insulin-treated group as compared to the diet-treated group after adjustment for age, gender, HbAlc, frequency of hypoglycemia, microangiopathy, macroangiopathy, and social support. In another study of 213 patients, MMSE scores were similar among treatment groups, while attention and learning were most impaired in insulin-treated groups after adjustment for age, gender, HbAlc, and duration of diabetes. Although the mechanism for the association between insulin treatment and cognitive impairment is unknown, hyperglycemia, hypoglycemia, and cerebral complications in insulin-treated patients may be possible explanations. Whatever mechanism may be involved, hypoglycemia should be considered especially if unexpectedly low HbAlc (< 6.5%) is observed or atypical neuropsychological symptoms appear. It is unknown how insulin withdrawal is successful in elderly diabetic patients. Using rapid or ultrarapid insulin injections three times daily, good glucose control achieved the goal of plasma glucose level of < 140 mg/dl before meals and at bedtime. Then, insulin therapy was converted to oral treatment of glimepiride (2 to 6 mg/day) and/or voglibose (0.6 mg/day) in 30 patients with poorly controlled Type 2 diabetes. About 83% of the patients were successful in the insulin withdrawal according to the criteria of HbAlc levels after two months < 8.0%. After removal of glucose toxicity, insulin withdrawal should be attempted to improve QOL in elderly patients with diabetes mellitus.     

Insulin therapy in insulin-dependent (type I) diabetes mellitus.

Intensive insulin therapy is suitable for individuals who want optimal glucose control and the least fluctuation in glucose levels. It permits a greater flexibility in life style and the opportunity to vary, within certain limits, meal and exercise schedules and meal content. This therapeutic approach is modeled on physiologic insulin secretion, but shortcomings in the subcutaneous route of delivery hamper the ability to control precisely the glucose levels. The therapy is most successful when the user is motivated to do the glucose monitoring and carbohydrate counting and educated to make rational decisions about how to adjust the insulin doses.     

Insulin pump therapy in type 1 pediatric patients: now and into the year 2000

There are a number of medical conditions such as growth failure in children, pregnancy, lipid abnormalities, and early complications that are improved by the meticulous glycemic control that can be achieved with insulin pump therapy (CSII). By using an insulin pump, many patients with severe hypoglycemia, the dawn phenomenon, extremes of glycemic excursion, recurrent diabetic ketoacidosis (DKA) and hypoglycemia unawareness have amelioration of these problems. However, pump therapy involves problems such as weight gain, recurrent ketosis due to pump failure, infections, and risk of hypoglycemia. Owing to many developmental issues, young children may not be able to wear the pump without parental supervision. We have used the pump at night time only in these patients. This has allowed children of 7-10 years of age to benefit from improved nocturnal glycemia without the risk of pump therapy when they are without an adult to help. We have also used the pump in subjects with recurrent DKA and in our general patient population (mean age 13.6+/-3.9 years). In our pump cohort, CSII led to improvement in quality of life, knowledge, adherence, and responsibility. A reduction in hypoglycemia, DKA rate and mean HbA(1c) was associated with pump usage. For this to occur, however, pump education must be geared to the pediatric subject and his/her family. Education materials and tools help in learning how to use the pump and how to deal with the intricacies of basal and bolus dosing, and the effect of exercise, food and illness on diabetes management. The pump has improved since it was first introduced and these modifications have made it easier, more painless and less hazardous. With the development of continuous glucose sensors and implantable pumps, the next century will see pump therapy lead to the artificial pancreas.     

Insulin resistance,hypertension and microalbuminuria in patients with Type 2 (non-insulin-dependent) diabetes mellitus

Summary We examined the impact of hypertension and microalbuminuria on insulin sensitivity in patients with Type 2 (non-insulin-dependent) diabetes mellitus using the euglycaemic insulin clamp technique in 52 Type 2 diabetic patients and in 19 healthy control subjects. Twenty-five diabetic patients had hypertension and 19 had microalbuminuria. Hypertension per se was associated with a 27% reduction in the rate of total glucose metabolism and a 40% reduction in the rate of non-oxidative glucose metabolism compared with normotensive Type 2 diabetic patients (both p<0.001). Glucose metabolism was also impaired in normotensive microalbuminuric patients compared with normotensive normoalbuminuric patients (29.4±2.2 vs 40.5±2.8 mol · kg lean body mass^–1 · min^–1; p=0.012), primarily due to a reduction in non-oxidative glucose metabolism (12.7±2.9 vs 21.1±2.6 mol · kg lean body mass^–1 ·min^–1; p=0.06). In a factorial ANOVA design, however, only hypertension (p=0.008) and the combination of hypertension and microalbuminuria (p=0.030) were significantly associated with the rate of glucose metabolism. The highest triglyceride and lowest HDL cholesterol concentrations were observed in Type 2 diabetic patients with both hypertension and microalbuminuria. Of note, glucose metabolism was indistinguishable from that in control subjects in Type 2 diabetic patients without hypertension and microalbuminuria (40.5±2.8 vs 44.4±2.8 mol · kg lean body mass^–1 · min^–1). We conclude that insulin resistance in Type 2 diabetes is predominantly associated with either hypertension or microalbuminuria or with both.     

Subclinical diabetic neuropathy: similarities between electrophysiological results of patients with Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes mellitus

Summary Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients share many clinical and biochemical characteristics. However, sural nerve biopsies from patients with advanced and chronic neuropathy show ultrastructural differences between these two groups. We investigated whether at a subclinical stage of the illness, when Type 1 and Type 2 diabetic patients are clinically uniform and the histopathological nerve alterations are not advanced, comparison between the two diabetes groups might show differences in nerve fibre involvement related to the different pathogeneses of the neuropathies. A total of 88 diabetic patients (52 Type 1 and 36 Type 2), with a subclinical form of polyneuropathy were selected. The clinical neurophysiological examination consisted of motor and sensory nerve conduction studies, Hoffmann (H)-reflex, single fibre electromyography and static as well as dynamic pupillometry. With regard to clinical neurophysiological abnormalities, the severity of the polyneuropathy appeared to be equal in both groups. Despite the absence of clinical symptoms the neurophysiological abnormalities were pronounced and it was impossible to differentiate Type 1 diabetic patients from Type 2 diabetic patients on a clinical neurophysiology basis when correcting for differences in age, height, and duration of illness. In the Type 1 diabetic group as well as in the Type 2 diabetic group the autonomic nerve fibres and nerves in the legs were more frequently affected than the thick myelinated nerves in the arms. These findings do not support the assumption that there is a difference in the manifestation of polyneuropathy between Type 1 and Type 2 diabetic patients.     

Glucagon-like peptide (GLP)-1 and leptin concentrations in obese patients with Type 2 diabetes mellitus.

AIMS: To assess differences in circulating leptin and glucagon-like peptide (GLP)-1 concentrations before and after an oral glucose load, in euglycaemic and isoinsulinaemic conditions, between obese patients with and without Type 2 diabetes mellitus. METHODS: Ten male obese (body mass index (BMI) > 30 kg/m2) patients with Type 2 diabetes and 20 matched non-diabetic subjects were studied. Leptin, GLP-1(7-36)amide and GLP-1(7-37) concentrations were measured 0, 30, 60, and 90 min after a 50-g oral glucose load administered 90 min after the beginning of a euglycaemic hyperinsulinaemic clamp. RESULTS: GLP-1(7-36)amide concentrations before the glucose load were significantly lower in diabetic patients than in controls (median (quartiles): 50.5 (44.7-53.2) vs. 128.7(100-172.5) pg/ml; P < 0.01), while no difference was observed in baseline GLP-1(7-37). In non-diabetic subjects, GLP-1(7-36)amide and GLP-1(7-37) concentrations increased significantly after the oral glucose load, while no glucose-induced increase in GLP-1 concentration was observed in diabetic patients. GLP-1(7-36)amide at 30, 60, and 90 min, and GLP-1(7-37) at 30 min, of the glucose challenge, were significantly lower in diabetic patients. Leptin concentrations were not significantly different in diabetic patients when compared to non-diabetic subjects, and they did not change after the oral glucose load. DISCUSSION: Leptin concentrations are not significantly modified in obese Type 2 diabetic patients. GLP-1(7-36)amide baseline concentrations are reduced in Type 2 diabetes; moreover, diabetic subjects show an impaired response of GLP-1 to oral glucose in euglycaemic, isoinsulinaemic conditions. This impairment, which is not the result of differences in glycaemia or insulinaemia during assessment, could contribute to the pathogenesis of hyperglycaemia in Type 2 diabetes mellitus.     

Proximal glomerulo-tubular balance in patients with Type 1 (insulin-dependent) diabetes mellitus

Summary To evaluate the glomerulo-tubular balance of sodium and water in the proximal tubules of diabetic patients with elevated glomerular filtration rate, the renal plasma clearance of lithium and the glomerular filtration rate (⁵¹Cr-EDTA plasma clearance) were determined simultaneously in 11 ambulatory Type 1 (insulin-dependent) diabetic patients (aged 25–35 years) with no evidence of diabetic nephropathy and in 10 age-matched healthy subjects. The renal plasma clearance of lithium, which is a measure of flow from the proximal tubule into the thin descending limb of the loop of Henle, did not differ between diabetic and control subjects (28.9±4.0 versus 28.3±5.1 ml/min per 1.73m² surface area, mean±SD), whereas the glomerular filtration rate in the diabetic patients was significantly higher than in the control sub jects (136±10.2 versus 108±13.6 ml/min per 1.73m², p< 0.001). The same held true for the fractional reabsorption rate in the proximal tubules (78.7±3.2 versus 73.6±4.9%, p< 0.02). The results indicate that the elevation of the glomerular filtration rate in diabetic patients is associated with a parallel increase in the proximal reabsorption rate. This type of glomeralo-tubular balance implies that the flow of water and flux of sodium to the segments distal to the proximal tubule are kept constant during variations in the glomerular filtration rate.     

Increased aortic stiffness in patients with Type 1 (insulin-dependent) diabetes mellitus

Summary The biomechanical properties of aortic samples from patients with Type 1 (insulin-dependent) diabetes mellitus and age- and sex-matched control subjects were analysed using a materials testing machine. The specimens were prepared from tissue outside areas of visible atherosclerosis in order to discriminate between primary Type 1 diabetic alterations in the aortae and secondary changes due to increased atherosclerosis. We paid special attention to the correction of biomechanical parameters for differences in wall thickness and registration of specimen length values. In the Type 1 diabetic aortae a marked reduction was found in the extensibility and an increase in their stiffness. The reduced extensibility was correlated significantly to the duration of Type 1 diabetes. The pronounced alterations in the mechanical properties could not be explained by the increase in the wall thickness which was observed among the Type 1 diabetic patients and the alterations could not be correlated to the grade of atherosclerosis in the thoracic aorta. The results of the present study, therefore, strongly suggest that Type 1 diabetic patients develop alterations in the arterial connective tissue independent of the presence of atherosclerosis. Such primary alterations in the vessel wall may play a role in the pathogenesis of large vessel disease among these patients.     

Insulin receptor gene polymorphisms in Type 2 (non-insulin-dependent) diabetes mellitus

Summary The insulin receptor has been proposed as a candidate gene for the inherited defect in Type 2 (non-insulin-dependent) diabetes mellitus and we therefore studied three restriction fragment length polymorphic sites, two revealed with the enzyme Sst1 and one by Rsa1, using two insulin receptor cDNA probes in 131 Caucasian Type 2 diabetic patients and 94 control subjects. The frequency of the six alleles studied did not differ significantly between the two groups. However, one allele, a 6.2 kilobase Rsa1 fragment (R+), was found more frequently in those diabetic subjects (n=48) with a positive family history of diabetes (R+frequency=0.48) compared to those diabetic subjects (n=63) with a negative family history (R+frequency=0.34, p< 0.05). These results suggest that this polymorphism may be a linkage marker for the genetic defect in a subgroup of Type 2 diabetic patients with a positive family history.     

Insulin requirement in elderly patients with non-insulin dependent diabetes mellitus (NIDDM)

Diabetes mellitus in the elderly is mainly of the non-insulin dependent type (NIDDM). A large proportion of such patients are treated with insulin, after many years of therapy with oral hypoglycemic agents (OHA), on the assumption that these lose their efficacy with time. Moreover, many such patients are obese and show preserved insulin release. In the present study 45 obese subjects with NIDDM (14 under good metabolic control and 31 who presented hyperglycemia for at least 3 mo prior to testing) were placed on a strictly hypocaloric diet (800 Kcal/d) for 20 to 24 d. All of these patients had preserved insulin release. At the end of the trial, all the patients presented a significant reduction in body weight and a near normalization of the blood glucose profile, as well as a significant decrease both in the serum cholesterol and triglyceride levels and in the systolic blood pressure. On the basis of these results, insulin and OHA could be reduced in all the patients and suspended in some of these. The decrease in blood glucose levels was the same in all the patients regardless of the length of time that each had suffered from NIDDM. Five non-obese patients were placed on the same regimen, but the daily insulin dose could not be reduced. These data indicate that the majority of obese elderly patients with NIDDM are unnecessarily treated with insulin or with OHA, while diet alone would be sufficient to keep them under good metabolic control.     

Insulin intervention in slowly progressive insulin-dependent (type 1) diabetes mellitus

OBJECTIVE: We tested the hypothesis that insulin therapy rather than sulfonylurea (SU) treatment is preferable to reverse or preserve beta-cell function among patients with slowly progressive insulin-dependent (type 1) diabetes (SPIDDM) or latent autoimmune diabetes in adults. METHODS: This multicenter, randomized, nonblinded clinical study screened 4089 non-insulin-dependent diabetic patients for glutamic acid decarboxylase autoantibodies (GADAb). Sixty GADAb-positive non-insulin-requiring diabetic patients with a 5-yr duration or shorter of diabetes were assigned to either the SU group (n = 30) or the insulin group (n = 30). Serum C-peptide responses to annual oral glucose tolerance tests were followed up for a mean of 57 months. The primary endpoint was an insulin-dependent state defined by the sum of serum C-peptide values during the oral glucose tolerance test (SigmaC-peptide) less than 4 ng/ml (1.32 nmol/liter). RESULTS: The progression rate to an insulin-dependent state in the insulin group (three of 30, 10%) was lower than that in the SU group (13 of 30, 43%; P = 0.003, log-rank). Longitudinal analysis demonstrated that SigmaC-peptide values were better preserved in the insulin group than in the SU group. Multiple regression analysis demonstrated that insulin treatment, a preserved C-peptide response, and a low GADAb titer at entry were independent factors in preventing progression to an insulin-dependent state. Subgroup analysis suggested that insulin intervention was highly effective for SPIDDM patients with high GADAb titers [> or =10 U/ml (180 World Health Organization U/ml)] and preserved beta-cell function [SigmaC-peptide > or = 10 ng/ml (3.31 nmol/liter)] at entry. No severe hypoglycemic episodes occurred during the study. CONCLUSIONS: Insulin intervention to preserve beta-cell function is effective and safe for patients with SPIDDM or latent autoimmune diabetes in adults.     

Transcapillary escape rate of albumin in hypertensive patients with Type 1 (insulin-dependent) diabetes mellitus

Summary Diabetic patients with elevated urinary albumin excretion rate (incipient or clinical nephropathy) also have an increased transcapillary escape rate of albumin. This study was designed to clarify whether this is caused by a general vascular dysfunction or by elevated systemic blood pressure. The systemic blood pressure and the transcapillary escape rate of albumin were measured in the following groups after 4 weeks without antihypertensive treatment: Group 1 — eleven healthy control subjects. Group 2 — ten Type 1 (insulin-dependent) diabetic patients with incipient nephropathy (urinary albumin excretion rate: 30–300 mg/24 h) and normal blood pressure. Group 3 — eleven non-diabetic patients with essential hypertension. Group 4 — nine Type 1 diabetic patients with hypertension but normal urinary albumin excretion (<30 mg/24 h). Group 5 — eleven Type 1 diabetic patients with nephropathy (urinary albumin excretion rate > 300 mg/24 h) and hypertension. Systolic and diastolic blood pressure were similar in the three hypertensive groups: group 3, 148±8/95±6; group 4, 150±12/94±8 and group 5; 152±12/92±7mmHg, but significantly elevated (p<0.001) compared to control group 1,117±12/74±9 and group 2, 128±7/82±4 mm Hg. The transcapillary escape rate of albumin was similar in the control subjects (5.2±2.7%) and the subjects in the normoalbuminuric groups 3 and 4 (6.2±1.9 and 5.1±1.4 %, respectively) and significantly lower (p<0.001) than in patients with elevated urinary albumin excretion without or with hypertension group 2, 10.1±2.8 and group 5, 11.4±5.7 %. The increased transcapillary escape rate of albumin in patients with elevated urinary albumin excretion is unrelated to moderate systemic hypertension and may therefore be caused by alterations in the properties of the capillary walls.     

A trial of nicotinamide in newly diagnosed patients with Type 1 (insulin-dependent) diabetes mellitus

Summary Various agents have been tried in subjects with newly diagnosed Type 1 (insulin-dependent) diabetes mellitus in an attempt to preserve Beta-cell function. In this double-blind study, nicotinamide or placebo were given for one year to 35 children and adolescents with newly-diagnosed Type 1 diabetes. All subjects were within six weeks of diagnosis and were between the ages of 6 and 18 years. Nicotinamide, a poly-(ADP-ribose) synthetase inhibitor, was given in a dose of 100 mg/year of age up to a maximum of 1.5 g/day. There were no initial differences between the 17 control and the 18 test subjects in relation to mean age, sex distribution, or severity at onset. Mean insulin dosages and HbA₁ values were similar for the two groups during the year of study. Fasting and glucagon-stimulated C-peptide levels were similar for the control and nicotinamide treated groups at the beginning and after 4 and 12 months. There were no differences in remission rates between the two groups. Nicotinamide, at this dosage, does not preserve residual insulin secretion in subjects with newly diagnosed Type 1 diabetes.     

Insulin pump therapy for type 1 diabetes treatment in a girl with Down's syndrome

We present the case of a 29.5-year-old girl with Down's syndrome, type 1 diabetes mellitus (DMT1), autoimmune thyroiditis and celiac disease starting on insulin pump therapy. After 22-month follow-up hemoglobin A1c dropped from 9% to 6.8%, even with a lower insulin requirement and no change in BMI.