Daily Insulin Requirement Research Articles

The Deadly Triad

The Deadly Triad

Helicobacter pylori infection and insulin requirement among children with type 1 diabetes mellitus.

Helicobacter pylori induces gastric inflammation and the the production of cytokines in infected individuals. Theoretically, this increased production of cytokines could be deleterious for the control of the glycemia of patients with diabetes. This study aimed to describe the insulin requirement among patients with type 1 diabetes and H pylori infection compared with uninfected counterparts. Cross-sectional design. Demographic information (age, gender, race, annual family income, and number of individuals per room in the household) and clinical information (age at diagnosis of diabetes, duration of illness, weight, height, compliance with clinical appointments, daily insulin units per kilogram of body weight [IU/kg/d], and glycosylated hemoglobin A level) was obtained from children and adolescents with diagnosis of type 1 diabetes mellitus who were seen at Children's Hospital in New Orleans. A total of 2 mL of blood was also collected and sera were tested for H pylori-specific immunoglobulin G antibodies using an enzyme immunoassay. The daily insulin requirement among infected and uninfected children was compared, and the effect of other variables was evaluated with multiple linear regression. Of the 71 subjects who were evaluated (median age: 11 years), 11 (15.5%) were found to be infected. H pylori infection was more frequent among subjects who were older, who had a lower family income, and who were black. Infected children were found to require more insulin (1.2 vs 0.9 IU/Kg/d) and their glycosylated hemoglobin A level was higher (14.9 vs 11.8) than the level found in uninfected subjects. Multiple linear regression analysis identified H pylori infection duration of illness, race (black), body mass index, and gender (female), to be associated independently with increased daily insulin requirement (IU/kg/d). n our study population, children with type 1 diabetes and H pylori infection had an increased daily insulin requirement compared with the requirement of their uninfected peers. The reason for this association requires additional investigation.

Dietary treatment of diabetic nephropathy with chronic renal failure.

Thirty-two patients with diabetes mellitus (22 IDDM and 10 NIDDM, 21 males and 11 females, age 44+/-11.8 years) were followed for 5.2+/-3.8 years after the onset of chronic renal failure, with the aim of evaluating the effect of low protein diets on the rate of decline of the residual renal function. During the 1.8+/-1.6 year follow-up period on free or uncontrolled low protein diet the mean rate of decline of creatinine clearance was 0.9+/-0.6 ml/min/month, significantly greater than that observed during 3.7+/-3.1 years on low or very low protein diets. The reduction of protein intake was followed by a significant decrease in daily urinary protein loss. A better glycaemic control was obtained on the low protein diet, and the daily insulin requirement decreased. The anthropometry, as well as the serum concentrations of rapid turnover proteins, did not change, in spite of the low or very low protein dietary supply for a long duration. The values of mean arterial pressure were quite similar during the follow-up period on free or uncontrolled low protein diet and during the study period on the low protein diet. A good compliance with reduced dietary intake (as demonstrated by the measurement of the daily urea excretion) was obtained in a large number of patients. In conclusion, our study confirms the protective effect on the residual renal function of low protein diets in IDDM and NIDDM patients with chronic renal failure due to diabetic nephropathy, in the absence of any sign of protein malnutrition.

Elevated sodium-lithium countertransport activity in erythrocytes is predictive of the development of microalbuminuria in IDDM.

Pathogenetic mechanisms other than the quality of metabolic control may play a role in the development of diabetic nephropathy. Some cross-sectional studies have shown that elevated erythrocyte sodium-lithium countertransport (Na+/Li+ CT) activity may be linked to incipient or overt nephropathy in insulin-dependent diabetic (IDDM) patients. The aim of the present work was to ascertain if high erythrocyte Na+/Li+ CT activity anticipates the development of microalbuminuria in IDDM patients. Evaluation of this cation transport system was carried out in 159 normotensive, normoalbuminuric IDDM patients, who were divided into two groups: those with values above (Group A) and those with values below (Group B) the median level in the overall population (300 mumol/erythrocytes x h). A total of 79 patients in Group A and 80 in Group B underwent periodic examinations over a similar time period (5.2 years, range 3.3-7.4 years and 5.4 years, range 3.4-7.5 years, respectively). Median sodium-lithium countertransport activity was stable when evaluated after 2 and 4 years of follow-up. Only seven patients were excluded from the protocol because changes in their sodium-lithium countertransport activity placed them on the other side of the median value with respect to their baseline measurement. Thus, 152 patients completed the study (76 in Group A and 76 in Group B). Of the 76 patients in Group A, 17 developed persistent microalbuminuria (22.3%). The number of patients in Group B showing persistent microalbuminuria was significantly lower (4 of 76; 5.2%; p < 0.01). The sensitivity of erythrocyte Na+/Li+ CT in predicting the development of microalbuminuria was 85% and its specificity was 55%. Seven patients of Group A and five of Group B developed arterial hypertension. Subjects in Group A had significantly higher mean HbA1c values of twice yearly measurements than those in Group B (9.6 +/- 1.7 vs 8.3 +/- 1.7%, p < 0.002, mean +/- SD) despite similar daily insulin requirements. Systolic and diastolic blood pressure levels were also evaluated every 6 months and were significantly higher in the Group A than in the Group B patients, although on average within the normal range. The odds ratio for developing persistent microalbuminuria in IDDM with elevated baseline erythrocyte Na+/Li+ CT activity after adjustment for gender and baseline albumin excretion rate, and mean 6 monthly plasma creatinine, HbA1c and systolic and diastolic blood pressure levels was 4.2 (95% confidence intervals 2.0-11.1). It was also found that the percentage of offspring having both parents with Na+/Li+ CT activity above the median value was significantly higher in Group A than in Group B (Group A vs Group B: 35 vs 19%; p < 0.01). On the contrary the percentage of offspring whose erythrocyte Na+/Li+ CT was lower in both parents was lower in Group A than in Group B: 10 vs 38%, p < 0.01). Parents of Group A offspring had arterial hypertension more frequently than those of Group B. These results indicate that erythrocyte Na+/Li+ CT activity is a useful diagnostic tool in identifying normotensive, normoalbuminuric patients who may be predisposed to develop persistent microalbuminuria. This disorder in the cation transport system is associated with poor metabolic control, higher blood pressure, and male sex; it also appears to be, at least partly, genetically transmitted.

The Rubenesque pregnancy: a progression towards higher blood pressure correlates with a measure of endogenous and exogenous insulin levels.

Women with gestational diabetes tend to progress to noninsulin-dependent diabetes (NIDDM) with a high cumulative incidence relative to the general population. These women have also been shown to be insulin resistant and may represent a variant of the insulin resistance syndrome or Syndrome X. Our previous studies indicated that administered insulin was associated with an increase in blood pressure in women with gestational diabetes, raising the question that insulin levels per se contribute to blood pressure in these women. We developed a means by which the insulin levels of a given pregnant individual might be estimated called the Fraction of Circulating Insulin Level Relative to Normal (FOCILRN = C-PEPTIDE/2.0 + TOTAL DAILY INSULIN DOSE/CALCULATED DAILY INSULIN REQUIREMENT BASED ON WEIGHT AND GESTATIONAL WEEK). The formula was applied to 15 nonhypertensive pregnant women of comparable obese phenotype (Rubenesque) with varying degrees of glucose tolerance (4 normal, 5 gestational diabetes treated with diet alone, 4 gestational diabetes treated with insulin, and 2 noninsulin-dependent diabetes). Blood pressure was quantified at the beginning of the study (gestational weeks 24-34) and again 4-8 weeks later using a 24-hr monitor. Correlation analysis was used to test for a relationship between the FOCILRN and blood pressure. The increase in mean arterial pressure was found to be continuous and linear with increasing insulin exposure as quantified by FOCILRN. The correlation was significant for all subjects (r = 0.961, p < 0.001) and remained significant even with removal of patients with NIDDM (r = 0.857, p < 0.001). The nighttime heart rate, systolic and diastolic blood pressures were found to be significantly correlated with FOCILRN (r = 0.651, p < 0.01, r = 0.724, p < 0.001, and r = 0.831, p < 0.001, respectively). The difference between the maximum and minimum diastolic blood pressure values between 12:00 AM and 6:00 AM between sessions 1 and 2 significantly differed among the groups with women on insulin having the highest FOCILRN having the least variation in blood pressure. In nonhypertensive women of obese phenotype (Rubenesque), increasing insulin exposure is associated with increasing mean arterial blood pressure and less variability of nocturnal blood pressure. These data provide support for the hypothesis that insulin may mediate blood pressure response in genetically vulnerable individuals. The identification of the Rubenesque phenotype during gestation may be a clinically useful marker for individuals at risk for Syndrome X.

A pilot study of chronic recombinant interferon-alfa 2a for diabetic proliferative retinopathy: Metabolic effects and opthalmologic effects

The objective of this study was to evaluate the metabolic effects and opthalmologic effects of α-interferon therapy in diabetes mellitus patients with proliferative diabetic retinopathy (PDR). Three volunteer patients [insulin-dependent diabetes mellitus (IDDM), insulin requiring non-insulin-dependent diabetes mellitus (NIDDM), and maturity onset diabetes of the young (MODY)] threatened with blindness due to progressive PDR were treated with a interferon for 4 months and were evaluated at intervals of 1–2 weeks to monitor the drug effects on carbohydrate tolerance and possible beneficial therapeutic effects on the preexisting PDR. Metabolic studies included basal and postsustacal glucose, c-peptide and glucagon, fasting serum cortisol, free fatty acids, growth hormone, insulin-like growth factor-1, and urinary microalbumin excretion. Ophthalmologic studies included visual acuity, slit lamp examination, gonioscopy, fluorescein angiography, and standard colored fundus photographs. In all subjects, hyperglycemia worsened with duration of increasing dosage of interferon therapy, requiring progressively higher daily insulin requirements of 17%–68% above pretreatment values. Lowered levels of stimulated C-peptide were observed in the NIDDM and MODY subjects. The counterregulatory hormones (cortisol, growth hormone, and glucagon) were elevated during the 4 months of interferon therapy. In all subjects, visual acuity appeared to stabilize. No new retinal hemorrhages occurred during the 4 months of interferon administration, although all subjects experienced hemorrhage within 6 weeks of termination of the drug. Although only three subjects were investigated, the 1–2 week frequency of metabolic and opthalmologic studies permit some conclusions. The metabolic effects of α interferon in our diabetic subjects were consistent worsening of carbohydrate tolerance associated with impaired β-cell secretion and increased insulin resistance. The extensive opthalmologic investigation suggested protection from retinal hemorrhage while receiving interferon, but further studies are indicated to validate these proposed and antiangiogenic properties.

Effect of directly ultraviolet-irradiated allografts of fetal pancreas in experimental diabetic dogs.

The proliferative responses of UV-irradiated islets from fetal pancreas decreased to 53.8 +/- 4.7% (mean +/- SEM) compared to that of UV-irradiated islets by allogeneic mixed islet-cell lymphocyte culture. In 5 pancreatectomized dogs, UV irradiated fetal dog pancreas was transplanted either into omentum pouches or the spleen without immunosuppressive agents. The diabetic status (daily insulin requirement for hyperglycemia, decrease in body weight, urine glucose) improved in dogs after allo-transplantation. The survival time after total pancreatectomy was significantly longer in allografted dogs than those treated only with daily insulin injections.

A Naltrexone-Induced Increase in Insulin Requirement

Nalurexone was used in an experimental treatment of anorexia nervosa in a patient who also had insulin.dependent type I diabetes. Naltrexone increased the insulin requirement, in this longitudinally controlled case study, the daily mean blood glucose and insulin requirement were followed through four periods (5 days each) no drug, drug, no drug and drug. There were no significant differences in blood glucose (p<0,05), but the daily insulin dose was higher in the drug than the non-drug periods being 52.8 + 1.8 and 61.4 + 3.3 units/day for control periods ! and 3 and 7 i.4 :!: 5.9 and 76.0 + 6.9 units/day for naltrexone periods 2 and 4, respectively, The differences between naltrexone and control periods were statistically significant at ix0.005 and<0.01. This interaction should be considered when using naltrexone in any diabetic patient, whatever the disorder being treated by the naltrexone. Moreover, since there was no endogenous insulin secretion in this patient, the effect must have been on insulin action rather than release. Opiate modulation of insulin action has not been previously, reported, although a number of effects of opiates on insulin release are known.

Continuous Subcutaneous Insulin Infusion

Continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI) represent two strategies of intensive insulin therapy, obtaining a strict metabolic control. The importance of such rigorous metabolic control in reducing the frequency and severity of diabetes long-term complications was highlighted by the Diabetes Control and Complication Trial (DCCT).To review the experience in the use of ISCI at Hospital São João, comparing it with the therapeutic modality of MID, regarding metabolic control, weight and body mass index (BMI), microalbuminuria, frequency of adverse events, lipid profile and quality of life.This retrospective, observational study included 25 type 1 diabetic patients followed-up on Endocrinology outpatient at Hospital São João, receiving CSII for more than 3 months after they were treated with MDI also for a period exceeding 3 months. For both periods of treatment, clinical data were obtained on the quality of glycaemic control (assessed by the levels of glycated hemoglobin--A1c), lipid profile, weight and body mass index (BMI) and microalbuminuria. To evaluate the impact on quality of life we used the ADDQoL questionnaire. A questionnaire was also used to determine the frequency of adverse events (severe hypoglycemia and ketoacidosis).The sample of 25 subjects with mean age of 33.35 ± 9.59 years, with a duration of disease, on average, of 17.1 ± 8.15 years and receiving ISCI for an average of 2.48 ± 1 08 years, obtained a decrease of 1.1% (p = 0.001) on the median value of A1c between 3 and 6 months of treatment when compared to MDI, reduction sustained throughout the analyzed period. The variation of the daily insulin requirements after pump placement was 12.75 units of insulin (p = 0.015), equivalent to a decrease of 0.20 units/kg (p = 0.023). The median of the distribution of BMI decreased 0.48 kg/m2 (p = 0.507) during CSII. The parameters of lipid profile and microalbuminuria showed no trend upward or downward after institution of CSII. The score obtained in the ADDQoL questionnaire was greater with CSII, the difference between the medians of the score distribution, before and after pump placement, was 0.056 (p = 0.92). There was a subjective perception of reduced frequency of adverse events with ISCI.The introduction of CSII allowed optimization of metabolic control, reduction of the daily insulin requirements and achievement of a higher level of satisfaction with no change in lipid profile, no weight gain and without increasing the frequency of adverse events.

Immunological resistance to human biosynthetic insulin — effects of immunosuppression and plasmapheresis

A 55-year-old gentleman, after being treated for a short time with a diet and with Chlorpropamide, was switched to purified porcine insulin due to ketonuria and ketoacidosis. After a year the patient developed immunological insulin resistance (mean daily insulin dose: 3.72 U/kg body weight; anti-insulin antibodies 78%). In order to lower anti-insulin antibodies human recombinant DNA insulin was introduced into further therapy. Contrary to expectations, the patient did not reduce whatsoever his anti-insulin antibodies and his daily insulin dose increased up to 5.63 U/kg body weight. Introduction of combined immunosuppressive therapy (prednisone plus azathioprine) together with plasmapheresis resulted in rapid lowering of daily insulin requirement and reduction in anti-insulin antibodies. Immunosuppressive therapy was continued with 10 mg of prednisone and a year later the patients insulin daily requirement was 0.66 U/kg BW while his antibodies were 18%. The possible causes of insulin resistance to human recombinant DNA insulin are discussed as well as the advantage of combined immunosuppressive therapy together with plasmapheresis that was used for rapid lowering of insulin daily requirement and anti-insulin antibodies titer.

Monitoring daily insulin needs--an important follow-up parameter in late pregnancy in diabetic mothers?

Pregnancy is a state of natural insulin resistance, which is due to placental production of human placental lactogen (HPL), an insulin antagonising hormone, leading to a remarkable increase of insulin requirement in pregnant diabetics in the 2nd and 3rd trimester. Aim of the prospective study was the quantification of daily insulin requirement during the last 28 days before delivery in pregnant women suffering from insulin-dependent diabetes mellitus (n = 20) with and without evidence of "placental insufficiency syndrome" employing peripheral rheography as indirect parameter for placental haemoperfusion. All diabetic women included controlled carbohydrate metabolism by means of a functional insulin therapy (FIT; HbA1c in normal range < 5.8%), a multiple injection regime with frequent blood glucose self-control at least from the 2nd trimester of pregnancy. According to the results of peripheral rheography in the 34th gestational week, an impedanceplethysmographic method for quantifying peripheral haemoperfusion, patients were subdivided in a group with (B: n = 8) and without (A: n = 12) indirect evidence of placental dysfunction. Groups did not differ in maternal age, duration of diabetes, maternal weight and week of delivery (A: 39.08 +/- 1.44; B: 39.12 +/- 1.46). Mean weight of neonates was lower in group B (3319 +/- 619 g) compared to group A (3613 +/- 437 g). During a comparable state of near-normoglycaemia in both groups, 7 out of 8 women in group B, but only 1 out of 12 women in group A displayed a significant decrease in daily insulin requirement from day -28 to day -3 before delivery (linear regression; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Beneficial effects of added glicazide in patients with type II diabetes mellitus treated with insulin

The aim of the study was to assess, in patients with non insulin dependent diabetes mellitus (NIDDM), either with previous failure to sulphonylureas or insulin treated since the disease started, if the combination of gliclazide to insulin therapy might induce a reduction of daily insulin requirement. 30 caucasian type II patients used to self-monitoring (11 female, 19 male, mean age 55.78 +/- 8.07) with residual pancreatic function (glucagon induced C-peptide release = 1.01 +/- 0.70 microgram/ml) entered the study. 8 were excluded for non compliance or for high antiinsulin antibodies levels and 4 are still under study. Each patients was given, for 3 months, 240 mg of gliclazide in addition to usual daily dose of insulin. Data presented as mean +/- s.e.m. were analysed with analysis of variance (p less than 0.05). Mean initial values of main parameters were as follows: glycaemia 192.7 +/- 33.1 mg/100 ml, insulinaemia 9.5 +/- 4.5 microUI/ml, daily insulin requirements 33.11 +/- 10.47 U/d, HbA1 C 7.5 +/- 1.7%. Total cholesterol 240.1 +/- 52.2 mg/10 ml, triglycerides 120.6 +/- 60.3 mg/100 ml. After 3 months treatment significant reduction in mean daily insulin requirements (20.78 +/- 16.15 U/d) was observed. In 13 patients (72.2%) while keeping good metabolic control (HbA1 C 7.46 +/- 1.63), insulin therapy was reduced (9 patients) or even stopped (4 patients). In the other 5, insulin was maintained or slightly increased. The increase in glucagon induced C-peptide release (1.41 +/- 0.99 micrograms/ml) did not reach significance, while glycaemia and insulinaemia were not changed (196.0 +/- 34.1 mg/100 ml, 11.02 +/- 5.05 microUI/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of metformin on haemorheology, lipid parameters and insulin resistance in insulin-dependent diabetic patients (IDDM)

We have evaluated the effect of metformin on haemorheology, lipid levels and insulin resistance in insulin-dependent diabetic patients over a 6-week period. Rheological parameters remained unaltered except for the whole blood clogging rate which decreased significantly. No effect on lipid levels was seen. The main effect of metformin was limited to daily insulin requirement and insulin units kg bw. Bearing in mind the negative effects of high insulin levels, metformin could be useful in the prevention of atherogenesis in insulin-dependent diabetic patients.

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.

Hypoglycaemia survey in insulin‐dependent diabetic population at time of change from beef to human insulin

AbstractA retrospective survey of 367 insulin‐dependent diabetics (IDDMs) showed that the risk of a diabetic experiencing hypoglycaemic coma in any one year during the previous five years was 7%. Of 123 who experienced one or more hypoglycaemic comas in the previous five years, only 35 (28%) experienced warning symptoms and only 97 (79%) were carrying glucose‐containing tablets or sweets at the time. A total of 279 (76%) regularly carried glucose at the time of the interview but only 92 (25%) were aware of glucagon and only 31 (8%) had it readily available.One‐hundred‐and‐twenty IDDMs were converted from beef to human insulins (Eli Lilly &amp; Co Ltd, Basingstoke) with no resultant change in daily insulin requirements nor in glycaemic control as assessed by HbAl measurements. Further assessment of hypoglycaemia was done after a mean of 6.8 months on human insulin. Fifteen (12%) felt reactive symptoms occurred more frequently compared with 70 (58%) who felt they were less common, and 12 (10%) felt they experienced less ‘adrenergic’ warning symptoms. Ten (8%) were treated for hypoglycaemic coma between the time of change from beef to human insulin and follow‐up. Forty‐one (34%) diabetics who changed to human insulins were more satisfied with the new preparation, 72 (60%) felt no difference and seven (6%) were less satisfied.

The relevance of persistent C-peptide secretion in type 1 (insulin-dependent) diabetes mellitus to glycaemic control and diabetic complications

The effect of residual C-peptide secretion in longer standing IDDM on glycaemic control and the prevalence and evolution of complications over 2 years was evaluated. Thirty-one subjects with IDDM of 15.4 (1.5) years duration (mean (SEM)) and residual C-peptide secretion, were matched for age, duration of diabetes and body mass index with 31 subjects without detectable C-peptide secretion. At trial entry and over 2 years, levels of HbA 1, fructosamine and mean blood glucose were essentially similar in both groups. Levels of glycated albumin (GSA) were significantly higher in the C-peptide negative group after 3 and 9 months ( P < 0.05). An increased prevalence of proliferative retinopathy in the C-peptide negative group and of peripheral vascular disease in the C-peptide secretor group was apparent at entry to the study (both P < 0.05), although no significant differences were observed after 1 or 2 years. There was no difference in the prevalence of peripheral or autonomic neuropathy, hypertension, nephropathy or ischaemic heart disease. Subjects with C-peptide concentrations greater than 0.100 pmol/ml at entry to this study had lower daily insulin requirements after 1 and 2 years, but behaved like the larger group with any detectable C-peptide secretion in all other respects. Residual C-peptide secretion was lost after 1 year in 7 patients, in whom glycaemic control during the year had been particularly poor. Insulin antibody titres were no different in the 2 groups at any time point. This study suggests that residual C-peptide secretion in longer standing IDDM confers the potential for limited improvements in glycaemic control. This effect appears to be insufficient to prevent the evolution of microvascular complications over a 2-year period. Resudual C-peptide secretion and relative hyperinsulinaemia may be associated with an excess of peripheral vascular disease.

Fasting Plus Prandial Insulin Supplements Improve Insulin Secretory Ability in NIDDM Subjects

To examine how insulin secretory ability is modified by strict glycemic control in non-insulin-dependent diabetes mellitus (NIDDM) subjects, basal and/or prandial insulin was supplemented for 4 wk in 24 diabetic subjects who were secondary failures to sulfonylurea treatment. One intermediate-acting insulin injection a day (n = 7) failed to suppress the rise in plasma C-peptide after meals and did not improve plasma C-peptide responses during a posttreatment oral glucose challenge. Continuous subcutaneous insulin infusion with a premeal bolus (n = 8) suppressed both fasting and meal-related rises in C-peptide and improved C-peptide response during the posttreatment oral glucose challenge. Daily insulin requirements during the 4 wk of treatment were reduced significantly by 52%. A short-acting insulin injection before each meal (n = 9) without basal supplementation suppressed the prandial rise in C-peptide and was associated with a significant reduction in daily insulin requirements during 4 wk of treatment by 28%. Diabetic subjects whose fasting and prandial hyperglycemia were less than 140 and less than 200 mg/dl, respectively, showed a significantly higher C-peptide response during oral glucose challenge after treatment than those whose insulin treatment only normalized (less than 200 mg/dl) prandial but not basal hyperglycemia (greater than 140 mg/dl). These results suggest that a short-term period of meal-related insulin treatment (which normalized prandial glycemia) increases residual beta-cell function in NIDDM subjects who failed long-term sulfonylurea administration. A basal insulin supplement alone was not effective. The effectiveness of a prandial insulin supplement may have been further improved by a combined basal and meal-related treatment program.

Dose-response effects of dietary marine oil on carbohydrate and lipid metabolism in normal subjects and patients with hypertriglyceridemia

Recent studies indicate that marine (ω-3) fatty acids decrease hypertriglyceridemia but worsen hyperglycemia in diabetes. We studied dose-response relationships between ω-3 intake and indices of carbohydrate and lipid metabolism in 21 hypertriglyceridemic patients with (n = 6) or without (n = 15) diabetes, and 6 normal volunteers. All subjects consumed isocaloric diets of 65% carbohydrate, 20% fat, and 15% protein. The basal diet contained 15% of total calories as vegetable oil (ω-6), and the test diets included 15%, 7.5%, or 3.75% calories as fish oil (MaxEPA). After three months of the basal diet, patients were randomized to receive two 3-month ω-3 diets in the following sequences: 15% 7.5% , 7.5% 15% , 7.5% 3.75% , or 3.75% 7.5% . Both 15% and 7.5% diets, regardless of sequence, significantly decreased serum triglycerides but increased low-density lipoprotein (LDL)-cholesterol levels as much as 98% and the LDL/high-density lipoprotein (HDL)-cholesterol ratio as much as 1.6-fold. Daily insulin requirements of three diabetic patients increased progressively while they received an ω-3-enriched diet for up to 2 years. In healthy controls, favorable changes induced by an ω-3 fatty acid diet in serum lipids and lipoproteins were associated with a tendency toward an inhibition of C-peptide secretion following a meal challenge. We conclude that substitution of commercially available ω-3 for ω-6 fatty acids improves hypertriglyceridemia but may worsen other lipoprotein indices and may increase insulin requirements in diabetic hypertriglyceridemic subjects.

Diabetes mellitus and Graves' disease in pregnancy complicated by maternal allergies to antithyroid medication

The pregnancy of a women with diabetes mellitus was complicated by Graves' disease and maternal allergies to propylthiouracil and methimazole. Preparations for surgical removal of the thyroid gland were being made until pregnancy intervened. Several well-documented mechanisms of hyperthyroidism, including increased intestinal absorption of glucose, decreased insulin responsiveness, and increased glucose production may exacerbate glucose intolerance; the daily insulin requirement of this patient rose 80% from her pregestational dosage. When large doses of propranolol failed to control her thyrotoxic symptoms and led to severe, recurrent hypoglycemic episodes, subtotal thyroidectomy was performed. A 42% decrease in insulin requirements was observed postoperatively, with return to the euthyroid state. A propensity for symptomatic postoperative hypoglycemia should be anticipated in diabetic patients undergoing thyroidectomy.

Chronic treatment with pirenzepine decreases growth hormone secretion in insulin-dependent diabetes mellitus.

We and others previously reported that nocturnal GH secretion in patients with insulin-dependent diabetes mellitus is blunted by acute cholinergic muscarinic blockade with pirenzepine. In this study, we investigated whether this inhibitory effect on GH secretion persists during chronic pirenzepine administration, and if pirenzepine administration affects glycemic control. Nocturnal GH secretion was studied from 2300-0800 h before and after one month of pirenzepine administration (100 mg/day, orally, given at 2300 h) in 13 diabetic patients receiving their usual insulin treatment. GH secretion (GH area under curve) was blunted after pirenzepine administration [mean, 877 +/- 215 (+/- SE) vs. 1407 +/- 311 micrograms/L.min; P less than 0.002]. During pirenzepine administration, hemoglobin A1c significantly decreased (P less than 0.02), and 4 of the 13 patients had lower daily insulin requirements (5-23 U/day), but there was no significant change for the group as a whole. These results indicate that the inhibitory effect of pirenzepine on GH secretion persists when pirenzepine is given chronically and that pirenzepine seems to improve the metabolic control of the patients.