Average Insulin Dose Research Articles

Exogenous insulin requirements do not differ between youth and adults with cystic fibrosis related diabetes

To examine whether insulin requirements and diabetes control differ between adolescents and adults with cystic fibrosis related diabetes (CFRD). All CFRD patients on insulin therapy seen at the University of Minnesota outpatient clinic from 1 January 2011 to 1 June 2012 were identified. Hemoglobin A1c (HbA1c) levels obtained during this period were averaged for each patient, and the most recent outpatient insulin dose was obtained. In addition, retrospective chart review was performed in order to obtain longitudinal data on insulin requirements during the transition from adolescence to adulthood. Eighteen youth aged 14-19 yr and 137 adults aged 20-67 yr were identified to be currently on insulin therapy. The average insulin dose was 0.38 ± 0.29 units/kg/d for adolescents and 0.46 ± 0.30 units/kg/d for adults (p = 0.20). In adults, insulin doses were significantly higher in transplant recipients: Tx = 0.58 ± 0.29, no Tx = 0.43 ± 0.30 (p = 0.005). Average HbA1c was 6.9 ± 2.1% in youth and 6.9 ± 1.5% in adults (p = 0.35). There were no changes in the insulin dosage when adolescents transitioned to adulthood with diabetes were not on higher doses of insulin compared to when they were adolescents with diabetes. Modest insulin requirements suggest the persistence of endogenous insulin secretion in both youth and adults with CFRD. In adolescents, residual endogenous insulin secretion likely compensates for the insulin resistance during puberty, keeping insulin requirements low.

Trough Insulin Levels in Bronchoalveolar Lavage Following Inhaled Human Insulin (Exubera) in Patients with Diabetes Mellitus

There are few data regarding insulin levels in the lungs during diabetes therapy with inhaled insulin. We examined the disposition of inhaled human insulin (Exubera(®) [EXU] human insulin [recombinant DNA origin], Pfizer, New York, NY) in the lungs by measuring trough insulin levels in bronchoalveolar lavage (BAL) fluid after 12 weeks of EXU treatment. After a 4-week run-in period of subcutaneous insulin therapy, 24 subjects with type 1 diabetes mellitus (T1DM) and 26 with type 2 diabetes mellitus (T2DM) continued their basal insulin regimen and received premeal subcutaneous (SC) insulin for 13 weeks, followed by 12 weeks of premeal EXU. BAL was performed approximately 12 h after the last insulin dose at (1) baseline, (2) following SC insulin, and (3) following EXU. Twenty patients with T1DM and 24 patients with T2DM completed all three bronchoscopies. BAL trough insulin levels were undetectable at baseline or following SC insulin. After EXU therapy, they increased to a median of 4.5 nM (1.6-9.0 nM) and 2.3 nM (0.5-9.4 nM) in T1DM and T2DM, respectively. BAL trough insulin levels did not correlate with treatment efficacy, adverse effects, plasma insulin levels, or changes in pulmonary function. A larger proportion of previous EXU doses was present in the BAL in patients with T1DM. We found no correlation between average daily insulin doses and BAL trough insulin levels. BAL trough insulin increased following EXU therapy, but this increase did not correlate with other clinical or laboratory parameters, suggesting no significant biological action. Further studies are warranted to better understand inhaled insulin deposition and clearance and possible effects of increased insulin levels on the lungs.

Insulin Glargine versus Insulin Detemir: Glycemic Control and Insulin Dose in Type 2 Diabetes Mellitus Patients Using a Medical Record Linkage System in the Netherlands

Background: In randomized controlled trials, patients with type 2 diabetes mellitus required higher doses of insulin detemir than insulin glargine to obtain the same glycemic control. However, this may differ in daily clinical practice. Methods: We conducted a cohort study to compare glycemic control, daily basal insulin dose and persistence in The Netherlands. Data were obtained from the PHARMO record linkage system. Patients starting glargine or detemir in 2004 through 2007 were included if they had a follow-up and history of at least 1 year, including glycated hemoglobin (HbA1c) measurements. Glycemic control and insulin dose were compared within 1 year after start of treatment. Average insulin dose was calculated based on the amount of insulin dispensed overtime. Results: A total of 708 patients on glargine and 298 on detemir were included. Patients starting glargine had less often used insulin in the previous year (19 versus31%, P<0.001) and less often used oral antihyperglycemic drugs concomitantly (61 versus67%, P<0.05) than those starting detemir. Despite a higher mean HbA1c at baseline in patients who started glargine (8.6% versus8.4%), the change from baseline in HbA1c at follow-up was greater with glargine (–0.9%) than with detemir (–0.4%, P<0.001). The proportion of patients with HbA1c < 7% was similar between the two cohorts. Mean insulin dose at follow-up was significantly lower with glargine than with detemir (31.3 IU versus 36.6 IU, P<0.01). Conclusions: Patients with type 2 diabetes mellitus who were treated with insulin glargine achieved better glycemic control with lower insulin doses than did patients who were treated with insulin detemir.

A Prospective Trial of U500 Insulin Delivered by Omnipod in Patients With Type 2 Diabetes Mellitus and Severe Insulin Resistance

To test the effectiveness and safety of U500 regular insulin delivered by continuous subcutaneous insulin infusion (CSII) via the Omnipod insulin delivery system in patients with uncontrolled type 2 diabetes mellitus and severe insulin resistance. In this prospective, 1-year, proof-of-concept trial, patients with insulin-requiring type 2 diabetes who had a hemoglobin A1c level of 7.0% or higher and severe insulin resistance (average insulin requirement, 1.74 units of insulin per kilogram each day; range, 1.4 to 2.64 units of insulin per kilogram [average insulin dose, 196.4 units daily]) were identified at routine office visits at Mountain Diabetes and Endocrine Center in Asheville, North Carolina, between December 2007 and August 2008. All patients had been on intensive insulin therapy with or without oral agents for more than 3 months. All patients were switched from baseline failed therapy to U500 regular insulin by continuous subcutaneous insulin infusion via Omnipod. Effectiveness was assessed by hemoglobin A1c measurement and 72-hour continuous glucose monitoring at baseline and at weeks 13, 26, and, 52 and by treatment satisfaction assessed by the Insulin Delivery Rating System Questionnaire at baseline and at week 52 while on U500 via Omnipod. Twenty-one adults were enrolled (mean age, 54 years; mean duration of diabetes, 4 years; mean body mass index, 39.4 kg/m2; mean insulin requirement, 1.7 U/kg per day; and mean hemoglobin A1c, 8.6%) whose previous treatment with U100 insulin regimens had failed. Twenty patients completed the study. Treatment with U500 insulin via Omnipod significantly reduced hemoglobin A1c by 1.23% (P<.001) and significantly increased the percentage of time spent in the blood glucose target range (70-180 mg/dL) by 70.75% as assessed by continuous glucose monitoring (P<.001) without a significant increase in hypoglycemia. Patients were satisfied with treatment with U500 insulin via Omnipod, and 14 patients elected to remain on treatment at study completion. U500 insulin delivered subcutaneously continuously via Omnipod is a safe and effective method of insulin delivery in the very insulin-resistant type 2 diabetic population.

PTH-089 Coeliac disease increases the risk of microvascular complications in patients with type 1 diabetes mellitus

Introduction There is an association between Coeliac disease (CD) and Type 1 diabetes however the effect of CD on important diabetes related outcomes is unknown. We previously identified 14 new cases of CD from a prospective study of patients with Type 1 diabetes (n=1000). We aimed to assess the effect of newly diagnosed CD on glycaemic control, lipid profile, renal function, retinopathy and peripheral neural function. Methods The CDDM patients (n=14) were age, sex, gender, weight and duration matched in a 2:1 ratio with patients having Type 1 diabetes alone (controls from the initial 1000 cohort). HbA1c, total cholesterol, HDL cholesterol, cholesterol:HDL ratio, triglycerides, eGFR and urinary albumin/creatinine ratio (aCR) were measured. Retinopathy was assessed through the annual eye screening programme. Peripheral nerve function was assessed by electrophysiological testing of 2 sensory and 2 motor nerves. Baseline values were recorded for both cases and controls and measurements repeated at 1 year in both groups. The CDDM group had been started on a gluten free diet. Results At baseline, there were no differences in age, duration, weight or average insulin dose (all p>0.1). Those with CDDM had higher HbA1c (8.2% vs 7.5%, p=0.05), lower total cholesterol (4.1 vs 4.9, p=0.014) and lower HDL cholesterol (1.1 vs 1.6, p=0.017) compared to controls. More patients with CDDM had abnormal urinary aCR (45.5% vs 4.8%, p=0.009) and higher nephropathy stage (p=0.009) compared to controls. There was no difference in the prevalence of retinopathy overall but higher grades of retinal damage were more common in CDDM (58.3% vs 25%, p=0.02). The prevalence of peripheral neuropathy was 42.9% in CDDM and 15% in controls (p=0.11). At 1 year follow-up, HbA1c levels and lipid profile were not significantly different between cases and controls. There were no differences in renal profile between cases and controls however eGFR dropped in those with CDDM (95.5 to 84.0, p=0.003) reflecting two patients having renal deterioration (one started dialysis). There were no differences in the prevalence of retinopathy from baseline but one patient with CDDM underwent retinal laser therapy. There were also no changes in the prevalence of neuropathy. Conclusion CD has an adverse effect on glycaemic control, HDL cholesterol, renal function and retinal status but not peripheral neuropathy. Following a GFD, glycaemic control and lipid profile improved but renal and retinal changes were still significantly worse compared to controls. This is the first study to observe these microvascular effects. Further research is required to determine whether earlier detection and treatment of CD limits these effects.

Efficacy of continuous glucose monitoring system combined with insulin pump in diabetic pafients aged 60 years and over

Objective To observe hypoglycemic efficacy of continuous glucose monitoring system (CGMS)combined with continuous insulin infusion(CSII)in the elderly diabetic patients aged 60 years and over.Methods A total 0f 100 elderly diabetic patients were randomly divided into two groups.50 were treated with CGMS or self-monitoring blood glucose(SMBG)and CSII.and whose insulin dose was adjusted based on results of monitoring,and the other 50 with SMBG and insulin pump as controls.whose insulin dose was adiusted based on the results of SMBG for three days.After two weeks.all the patients were monitored by CGMS for blood glucose.Results Mean blood level of glucose and mean amplitude of glycemic excursions(MAGE)were significantly lower in CGMS+CSII group than those in controls[(6.6±2.3)mmol/L vs.(7.5±2.1)mmol/L,and(3.9±0.9)mmol/L vs.(5.1±0.6)mmol/L,respectively,P＜0.05 1.Average insulin dose used was significantly lower in CGMS+CSII group than that in controls [(0.64±0.21)U/kg vs.(0.82±0.41)U/kg,P＜0.05],and duration of hypoglycemia was less in the former than that in the latter[(20±3)min vs.(40± 9)min,P＜0.05 ].Conclnsions CGMS combined with CSII can decrease blood glucose.glucose excursions.average dose of insulin and duration of hypoglycemia in the elderly diabetic patients,as well as prevent occurrence of hypoglycemia. Key words: Diabetes mellitus,type 2; Blood glucose self-monitoring; Insulin infusion system

Postprandial glycemic control using insulin aspart with NPH in inadequately controlled diabetics

To compare the efficacy and safety of insulin aspart (IAsp) and human insulin (HI) when applied as meal-time insulin with neutral protamine Hagedorn insulin (NPH) at bedtime in diabetics. A total of 220 Chinese subjects with type 1 or type 2 diabetes from 5 different hospitals were randomized by a ratio of 1:1 into two groups accepting IAsp or HI combined with NPH respectively. The main endpoints were assessed by fasting plasma glucose (FPG), 2 hour postprandial plasma glucose (2 h PPG), HbAlc and hypoglycemia. A greater reduction in mean 2 h PPG was achieved in the IAsp group [(14.6 +/- 5.3) mmol/L] as compared with the HI group [(8.4 +/- 4.1) mmol/L] (P < 0.01, adjusted for baseline value, center effect and diabetes type). Significantly more IAsp-treated subjects reached the 2 h PPG target (50.0% vs 25.5%, P < 0.01). HbA1c was reduced more in IAsp/NPH group [(9.3 +/- 1.4)% vs (7.7 +/- 1.3)%] than in HI/NPH group [(9.2 +/- 1.2)% vs (7.7 +/- 1.2)%]. HbA1c target was reached by 24.5% (IAsp) vs 14.5% (HI) of subjects (P < 0.05). No major hypoglycemia or serious adverse events were observed for the IAsp group. Lower incidence of nocturnal hypoglycemia (IAsp/NPH: 3% vs HI/NPH: 4%) was reported in the IAsp group. Average daily insulin doses were 0.60/0.23 (IAsp/NPH) and 0.65/0.24 (HI/NPH) IU/kg respectively. Treatment of IAsp in basal-bolus therapy in combination with NPH provides a superior postprandial glucose control and allows more subjects to reach the glycemic target without elevating the nocturnal hypoglycemic risk or adverse events.

Optimierung der glykämischen Kontrolle und Dosistitration mit Insulin Glargine (Lantus®) durch frei praktizierende Ärzte in der Schweiz: Resultate des OPTI-LAN Praxiserfahrungsberichtes

National and international societies have published guidelines regarding glycaemic control in type-2 diabetes mellitus. Clinical studies have shown that glycaemic control of type-2 diabetes mellitus can be improved using simple algorithms for titration of insulin Glargine (Lantus). It is unclear, to what degree published guidelines are adopted in daily practice in Switzerland. We performed a postmarketing study on the adoption of published guidelines regarding glycaemic control and the use of algorithms for titration of insulin Glargine doses by 77 general practitioners in Switzerland. Data collection was done prospectively over 6 months from September 2005 to September 2007. A total of 317 patients were included with a mean age of 63 +/- 11 years, 137 (43%) were female and 298 (94%) had type-2 diabetes. Average diabetes duration was 8 +/- 6 years. The initial average HbA1C and fasting plasma glucose were 8.9 +/- 1.6% and 10.1 +/- 3.2 mmol/l respectively. This, despite treatment with at least one oral hypoglycaemic agent (83% of patients) and/or insulin (47% of patients). As target the treating physicians chose an HbA1C < or = 7% for 284 patients (90%) and a fasting plasma glucose < or = 7 mmol/l for 245 patients (77%); thresholds that correspond to the guidelines of the Swiss Society of Endocrinology and Diabetes (SSED). The algorithm developed Riddle et al. was used by 33% of treating physicians; whereas 17% of physicians used a schedule proposed by the American Diabetes Association (ADA) and by the European Association for the Study of Diabetes (EASD) that is generally adapted by the patients themselves. During the 6-month treatment with insulin Glargine (Lantus) 196 patients (62%) achieved the SSED guidelines for glycaemic control. On average HbA1C was reduced by 2.1% (8.9 vs. 6.8%) and fasting plasma glucose by 3 mmol/l (10.1 vs. 7.1 mmol/l). On average insulin dose was increased by 14 IU (from 16 to 30 IU). Overall 91% of patients were satisfied with the way insulin doses were adapted. In 64% general wellbeing improved during the treatment period and in 27% it was unchanged. In daily practise in Switzerland the recommendations of the SSED are implemented to a high degree. Using insulin Glargine (Lantus) recommended goals of glycaemia can be rapidly and adequately achieved and patient satisfaction can be improved.

Switch to oral hypoglycemic agent therapy from insulin injection in patients with type 2 diabetes

We aimed to determine the feasibility of substituting thiazolidinedione-based therapy for insulin injection therapy in patients with type 2 diabetes. Thirty-six subjects (17 men and 19 women) aged 67.8 +/- 11.3 years with an average insulin dose of 0.46 +/- 0.17 U/kg bodyweight, a duration of insulin therapy of 6.1 +/- 8.2 years and an average hemoglobin A1c (HbA1c) of 6.8 +/- 1.3% were switched from insulin injection therapy to pioglitazone, glimepiride and voglibose combination therapy. The number of subjects achieving HbA1c levels of less than 7% at 4 months was 30. The success rate of switch therapy was 83% (30/36). HbA1c was significantly reduced from 6.7 +/- 1.3% to 5.9 +/- 0.7% at 4 months after the switch (P < 0.01) in 32 patients who completed the planned 4-month study. No adverse effects including heart failure, liver dysfunction or severe hypoglycemia were observed. The insulin dose and the maximum blood glucose on the switch day were significantly lower and the age was significantly higher in the subjects who achieved HbA1c less than 7% at 4 months compared to those who did not (P < 0.05). Thiazolidinedione-based oral combination therapy may efficiently and safely substitute relatively high-dose insulin injection therapy in patients with type 2 diabetes.

Insulin Requirements in the Intensive Care Unit in Response to Infection

Infectious complications in the intensive care unit (ICU) are classically identified when an elevated temperature triggers obtaining cultures. Elevated temperature, however, is a nonspecific marker of infection and may occur well into the course of the infection. The goal of this study was to evaluate whether escalating insulin demands may serve as an earlier marker for infection. A retrospective review of a prospective database from a trauma ICU over a 6-month period was done for all patients who developed infection while in the ICU. All patients in the ICU are placed at admission on an intensive insulin protocol with target blood glucose levels between 80 and 110 mg/dL. Data were collected on infection, insulin needs, blood glucose levels, temperature, white blood cell count, and antibiotic use. Twenty-four infections were identified, with 16 pneumonias, four bloodstream infections, and four urinary tract infections. Twelve of the 24 patients had increasing insulin needs in the 3 days preceding their infection diagnosis, with nine of the 12 requiring continued escalation of insulin needs from preinfection Day 3 to 2 to 1 (D3, D2, D1). In five of the 12 patients, the escalation of insulin dose preceded the elevated temperature, and in three of the 12 patients, the escalation preceded elevation of the white blood cell count above 12. For all 24 patients, the average insulin dose increased steadily, from 1.8 U/hr on D3 preinfection to 2.5 U/hr D2 and 3.1 U/hr D1. Infection does seem to be preceded by escalating insulin demands in many patients. A prospective study to evaluate the value of increased insulin demand as a marker for developing infection is warranted.

Model-Based Insulin and Nutrition Administration for Tight Glycaemic Control in Critical Care

Present a new model-based tight glycaemic control approach using variable insulin and nutrition administration. Hyperglycaemia is prevalent in critical care. Current published protocols use insulin alone to reduce blood glucose levels, require significant added clinical effort, and provide highly variable results. None directly address both the practical clinical difficulties and significant patient variation seen in general critical care, while also providing tight control. The approach presented manages both nutritional inputs and exogenous insulin infusions using tables simplified from a model-based, computerised protocol. Unique delivery aspects include bolus insulin delivery for safety and variable enteral nutrition rates. Unique development aspects include the use of simulated virtual patient trials created from retrospective data. The model, protocol development, and first 50 clinical case results are presented. High qualitative correlation to within +/-10% between simulated virtual trials and published clinical results validates the overall approach. Pilot tests covering 7358 patient hours produced an average glucose of 5.9 +/- 1.1 mmol/L. Time in the 4-6.1 mmol/L band was 59%, with 84% in 4.0-7.0 mmol/L, and 92% in 4.0-7.75 mmol/L. The average feed rate was 63% of patient specific goal feed and the average insulin dose was 2.6U/hour. There was one hypoglycaemic measurement of 2.1 mmol/L. No departures from protocol or clinical interventions were required at any time. Modulating both low dose insulin boluses and nutrition input rates challenges the current practice of using only insulin in larger doses to reduce hyperglycaemic levels. Clinical results show very tight control in safe glycaemic bands. The approach could be readily adopted in any typical ICU.

Intraperitoneal Alginate-Encapsulated Neonatal Porcine Islets in a Placebo-Controlled Study With 16 Diabetic Cynomolgus Primates

Background A nonhuman primate model of diabetes is valuable for assessing porcine pancreatic islet transplants that might have clinical benefits in humans. Methods Neonatal porcine islets, microencapsulated in alginate–polyornithine–alginate, were injected intraperitoneally (10,000 IEQs/kg islets) into eight adult male cynomolgus monkeys rendered diabetic with streptozotocin. Eight diabetic controls were given an equivalent dose of empty placebo capsules. All subjects received a repeat transplant 3 months after the first. Results The transplant was well tolerated and no adverse or hypoglycemic events occurred. There were two deaths from nontransplant treatment or diabetic complications unrelated to the transplants. After transplantation, the average insulin dose was reduced in the islet-treated group and increased in the control group. At 12 weeks after the first transplant there was a mean 36% (95% CI: 6% to 65%, P = .02) drop in daily insulin dose compared with the control group. After 24 weeks the difference increased to a mean of 43% (95% CI: 12% to 75%, P = .01) without significant differences in blood glucose values between the two groups. Individual responses after islet transplant varied and one monkey was weaned off insulin by 36 weeks. At terminal autopsy, organs appeared normal and there was no visible peritoneal reaction. No animal had polymerase chain reaction (PCR)-amplified signals of porcine endogenous retrovirus or exogenous virus infections in blood or tissues. Conclusion Repeated intraperitoneal transplantation of microencapsulated neonatal porcine islets is a safe procedure in diabetic primates. It was shown to result in a significant reduction in insulin dose requirement in the majority of animals studied, whereas insulin requirement increased in controls.

Insulin management and metabolic control of type 1 diabetes mellitus in childhood and adolescence in 18 countries. Hvidøre Study Group on Childhood Diabetes.

Insulin regimens and metabolic control in children and adolescents with Type 1 diabetes mellitus were evaluated in a cross-sectional, non-population-based investigation, involving 22 paediatric departments, from 18 countries in Europe, Japan, and North America. Blood samples and information were collected from 2873 children from March to August 1995. HbA1c was determined once and analysed centrally (normal range 4.4-6.3%, mean 5.4%). Year of birth, sex, duration of diabetes, height, body weight, number of daily insulin injections, types and doses of insulin were recorded. Average HbA1c in children under 11 years was 8.3 +/- 1.3% (mean +/- SD) compared with 8.9 +/- 1.8% in those aged 12-18 years. The average insulin dose per kg body weight was almost constant (0.65 U kg(-1) 24 h(-1)) in children aged 2-9 years for both sexes, but there was a sharp increase during the pubertal years, particularly in girls. The increase in BMI of children with diabetes was much faster during adolescence compared to healthy children, especially in females. Sixty per cent of the children (n = 1707) used two daily insulin injections while 37% (n = 1071) used three or more. Of those on two or three injections daily, 37% used pre-mixed insulins, either alone or in combination with short- and intermediate-acting insulin. Pre-adolescent children on pre-mixed insulin showed similar HbA1c levels to those on a combination of short- and long-acting insulins, whereas in adolescents significantly better HbA1c values were achieved with individual combinations. Very young children were treated with a higher proportion of long-acting insulin. Among adolescent boys, lower HbA1c was related to use of more short-acting insulin. This association was not found in girls. We conclude that numerous insulin injection regimens are currently used in paediatric diabetes centres around the world, with an increasing tendency towards intensive diabetes management, particularly in older adolescents. Nevertheless, the goal of near normoglycaemia is achieved in only a few.

Energy Intake and Glycemia in Lactating Women with Type 1 Diabetes

Objective To describe glycemia and insulin administration in lactating women with type 1 diabetes and compare their energy intake, lactation onset, and postpartum weight to lactating women without diabetes. Design A prospective observational study conducted at 2, 3, 6, 14, 42, and 84 days postpartum. Insulin dosage and glucose levels after fasting and at 80 and 110 minutes after eating (by measuring capillary blood glucose concentrations and glycated hemoglobin [HbA 1c] values) are described for women with type 1 diabetes. Dietary intake, weight, and lactation onset for women with type 1 diabetes are compared with those without the disease. Subjects/setting Fourteen lactating women with type 1 diabetes and 25 women without diabetes (control subjects) were recruited from private obstetrician offices and high-risk prenatal clinics at 3 major medical centers. Statistical analyses A repeated-measures 2-factor analysis of variance was used to determine group, time, and interaction effects between women with type 1 diabetes and the control group at 2, 3, 7, 14, 42, and 84 days postpartum. Results Seven women with type 1 diabetes breast-fed through 84 days postpartum, although they perceived later onset of milk and had fasting and postprandial hyperglycemia. Their HbA 1c levels increased by 20%, confirming relative hyperglycemia. After adjustment for prepregnancy weight, women with type 1 diabetes consumed 7 kcal fewer per kilogram per day than control subjects. Average insulin dose was returned to prepregnancy levels of 45.3±3.6 U/d (least square means±standard error of the mean) by 1 week. Application Achieving desired metabolic control during the establishment of lactation is difficult. A better understanding of energy and insulin needs and their relationship to lactation in women with type 1 diabetes is needed. J Am Diet Assoc. 1998; 98: 642–648.

Hypoglycemic action of an oral fig-leaf decoction in type-I diabetic patients

The effect of a decoction of fig leaves ( Ficus carica), as a supplement to breakfast, on diabetes control was studied in insulin-dependent diabetes mellitus (IDDM) patients (six men, four women, age 22–38 years, body mass index (BMI): 20.8±3.0 kg/m 2, HbA 1c 7.6±0.9% with a mean duration of diabetes of 9±6.3 years). The patients were managed with their usual diabetes diet and their twice-daily insulin injection. During the first month, patients were given a decoction of fig leaves (FC) and during the next month a non-sweet commercial tea (TC). The patients were divided into two groups ( n=5) with random allocation and cross-over design. A standard breakfast was given at the beginning and end of each month-run. C-peptide, 2 h pre- and post-prandial glycemia, HbA 1c, cholesterol, lipid fractions and hematology data, were analyzed during each visit. Glycemic profiles (7/day per week) were recorded by patients. Only two patients had intolerance dropout. Post-prandial glycemia was significantly lower during supplementation with FC 156.6±75.9 mg/dl versus TC 293.7±45.0 mg/dl ( P<0.001) without pre-prandial differences 145.0±41.5 and 196.6±43.2 mg/dl, respectively. Medium average capillary profiles were also lower in the two sub-groups of patients during FC 166.7±23.6 mg/dl, P<0.05 and 157.1±17.0 mg/dl versus TC 245.8±14.2 mg/dl and 221.4±27.3 mg/dl. Average insulin dose was 12% lower during FC in the total group. The addition of FC to diet in IDDM could be of help to control postprandial glycemia.

Growth parameters, growth hormone (GH) response to clonidine and circulating insulin-like growth factor-I (IGF-I), free thyroxine (FT4) and cortisol concentrations in relation to glycaemic control in children with insulin-dependent diabetes mellitus.

The objective of this paper was to determine the effect of glycaemic control and endocrine functions on linear growth in children with IDDM. We studied 45 prepubertal children with IDDM (30 males, 15 females) over 1 year period. The mean +/- SD for age of onset and duration of IDDM were 6.2 +/- 2.3 years and 3.5 +/- 1.3 years, respectively. At each clinic visit (every 3 months), glycaemic control was assessed by measuring glycosylated haemoglobin (HbA1C). Growth hormone and cortisol responses to high dose clonidine (0.15 mg/m2) and ACTH, respectively, were evaluated and circulating concentrations of free thyroxine (FT4) and TSH estimated. The average insulin dose (unit/kg/day) during this period was calculated for each patient. Growth was assessed by determining both height standard deviation score (HtSDS) and growth velocity standard deviation scores (GVSDS) and bone age determined according to the atlas of Greulich and Pyle. Two-hundred-and-fifty age- and sex-matched normal children served as controls for growth data, and 20 normal age-matched children and 20 normal children with short stature (NVSS) served as controls for the hormonal studies. Growth velocity (GV) (cm/year) and GVSDS were significantly lower in children with IDDM compared to normal children, and significantly lower in children with poorly controlled diabetes compared to those with good glycaemic control. GV and GVSDS were inversely correlated to HbA1C (r = -0.356, P < 0.01 and r = 0.335, P < 0.01 respectively). GVSDS was correlated with serum IGF-I (r = 0.22, P < 0.01), FT4 (r = 0.321, P < 0.01) and inversely with basal GH (r = -0.362, P < 0.01) concentrations, but was not correlated with cortisol levels or peak GH concentrations in response to clonidine. GVSDS was correlated with HtSDS (r = 0.222, P < 0.01) and inversely with age (r = -0.43, P < 0.05). There was no significant correlation between GVSDS on the one hand and weight gain or body mass index (BMI) on the other hand. Peak GH response to clonidine was correlated with BMI (r = 0.68, P < 0.001) and insulin dose/kg/day (r = 0.602, P < 0.01). This study confirms that in children with IDDM linear growth velocity is dependent on the age of the child and the degree of glycaemic control, as well as on growth promoting hormones such as IGF-I and FT4. High BMI is associated with more GH secretion in response to clonidine, this might explain the higher requirements of insulin/kg in children with IDDM and high BMI.

Insulin doses in children using conventional therapy for insulin dependent diabetes

The objective of this project was to develop plots of daily insulin dosages by percentile in diabetic children and to analyze various factors, such as metabolic control, age, and duration of diabetes that might influence the insulin prescription. Patients in extremely poor metabolic control (HbA 1c > 9.8%) and patients with less than 1 year of diabetes were excluded from analysis. Patients were aged 2–21 years and the mean age at diagnosis was 8 years. Thirty-two percent of the patients were younger than 5 years and 15% were older than 15 years at diagnosis. Ninety-nine percent of patients used both regular and intermediate-acting (NPH or Lente) insulin 10–30 min before breakfast and again in the evening. Ten percent of the patients used only regular insulin at supper but used intermediate-acting insulin at bedtime. Insulin doses varied between 0.3 and 1.2 U/kg/day in prepubertal children (mean, 0.8 U/kg/day) and 0.5 and 1.8 U/kg body weight/day in pubertal children (mean, 1.25 U/kg/day). Average insulin doses in boys and girls were similar, except at ages 10–13, when the dose was significantly higher in girls. The insulin dose declined after age 17 in both genders to a value at age 21 that was 20–30% lower than the highest dose during pubertal years. Insulin dose did not correlate with duration of disease after 2 years, the ratio of morning to evening insulin, the ratio of regular to intermediate-acting insulin, or body mass. There was a slight association between higher insulin doses and higher glycosylated hemoglobin values. The results indicate that insulin requirements vary over a wide range in a group of children with metabolic control ranging from ‘excellent’ to ‘fair’ and correlate primarily with age and pubertal development. About 25% of prepubertal children and 50% of pubertal and post-pubertal children use more than 1 U insulin/kg/day — a dose commonly believed to be an ‘upper limit’ by many health professionals. The data should provide guidelines for the range of insulin dosing required to achieve fairly good to excellent control in diabetic children of various ages.

Changes in Insulin Therapy During Pregnancy

Care of the diabetic pregnant woman requires a proper understanding of anticipated changes in insulin therapy as a guide for establishing and maintaining strict glucose control. Changes in daily insulin doses were reviewed for 58 pregnancies of 50 insulin-dependent women who were followed for 26 +/- 3 weeks (mean +/- 1 SD) before delivery. By late gestation, insulin was administered on two or three occasions each day using a combination of regular--and intermediate--acting preparations in 55 (95%) pregnancies. Regardless of the metabolic control and duration of diabetes, averaged daily insulin requirements increased twofold from earlier in pregnancy. Following initial hospitalization, insulin requirements often decreased before increasing almost linearly between 2 and 9 months gestation. Fluctuations in insulin requirements were greatest during the last trimester. Insulin demand dropped precipitously after delivery and was two-thirds the averaged prepregnancy insulin dose or one-third the dose at 9 months gestation by the third postpartum day. The total average insulin dose was the same as that before pregnancy by the end of the first postpartum week. Explanations for these changes in prescribing insulin are described.

Rate of insulin infusion with a minipump required to maintain a normoglycemia in diabetic rats.

It is notoriously difficult to normalize plasma glucose profiles for a prolonged time by conventional methods of insulin administration in both human and animal diabetics. The present study was conducted to determine the dosage of insulin needed to maintain prolonged and around-the-clock normoglycemia as well as normoglucagonemia in streptozotocin diabetic rats with the Alzet osmotic minipump which releases insulin constantly for 14 days. A minipump was inserted into the peritoneal cavity of diabetic rats under chloral hydrate anesthesia. Diabetic rats were treated with several consecutive minipumps and body weights, plasma glucose, and plasma glucagon levels were monitored. Plasma glucose concentrations were determined every 8 hr for several days and were found essentially identical during the active life of the minipump. An average insulin dose of 8.0 to 9.0 U/kg/day was required to normalize body weights, plasma glucose, and plasma glucagon of streptozotocin diabetic rats treated with the Alzet osmotic minipump Model 2002.

Hypolipidemic effects of high-carbohydrate, high-fiber diets

Serial measurements of serum cholesterol and triglyceride (TG) concentrations were performed in diabetic men fed high-carbohydrate, high-fiber (HCF) as well as high-carbohydrate, low-fiber (HCLF) diets. Fourteen lean men were first fed control diets for 1 wk and then fed weight-maintaining HCF diets (70% carbohydrate) that were restricted in fat and cholesterol. Average insulin doses dropped from 27 U/day on control diets to 12 U/day on HCF diets and fasting plasma glucose values were 26 mg/dl lower on HCF diets. On HCF diets, serum cholesterol values were lower by 32% (64 mg/dl, p < 0.001) than values on control diets. Fasting serum TG values were slightly lower on HCF diets but average postprandial TG values were significantly lower ( p < 0.001) on HCF diets than on control diets. In another study, 11 men were fed two weight-maintaining 70% carbohydrate diets in an alternating sequence; one diet was high in plant fiber (HCF) and the other was low in plant fiber (HCLF). Insulin doses averaged 20 U/day on control diets and fell to 11 U/day ( p < 0.01) on HCF diets or 12 U/day ( p < 0.01) on HCLF diets. Fasting serum TG values were similar on the control and HCF diets; on HCLF diets fasting serum TG values were higher by 28% (37 mg/dl) than values on control diets ( p < 0.01). Incorporation of generous amounts of plant fiber into the diet prevented the hypertriglyceridemic response to these high-carbohdrate diets. These studies also indicate that dietary maneuvers can be very effective in lowering serum cholesterol values in patients with diabetes mellitus.