Changes In Insulin Requirements Research Articles

Biosimilar Insulin and Insulin Antibodies

Biosimilar Insulin and Insulin Antibodies

Efficacy of Continuous Subcutaneous Insulin Infusion in Type 2 Diabetes Mellitus: A Survey on a Cohort of 102 Patients with Prolonged Follow-Up

We evaluated the long-term efficacy of continuous subcutaneous insulin infusion (CSII) for treating type 2 diabetes patients uncontrolled by multiple daily injections. All 102 type 2 diabetes patients who began insulin pump therapy at Caen University Hospital (Caen, France) between January 1998 and August 2008 were included in a retrospective observational study. Ninety-three percent of the patients were previously treated by insulin with a mean duration of 5.6 years. The median duration of follow-up with CSII was 24 months. A1c glycated hemoglobin (HbA1c) improved from baseline (9.3 ± 1.8%) to the 1-year evaluation (7.8 ± 1.4%) (P < 0.001). The magnitude of HbA1c improvement was highly dependent on (1) pretreatment HbA1c level, (2) degree of patient's autonomy, and (3) previous antidiabetes treatment. HbA1c decreased by 0.9 ± 1.6% (P = 0.002) in the group previously treated by a basal-bolus regimen. HbA1c decrease was maintained at follow-up until 6 years (P < 0.05). Mean body weight gain was 3.9 ± 8.6 kg at 1 year (P < 0.001) and remained stable at follow-up. No significant change in insulin requirement was observed. The use of CSII in patients with type 2 diabetes is safe and effective for improving glycemic control, particularly in those patients with baseline HbA1c above 8%. Such beneficial effect of CSII may persist until 6-year follow-up, suggesting the durability of CSII efficacy in our study population.

持続皮下インスリン注入療法（CSII）により妊娠・周産期・授乳期のインスリン必要量の推移を詳細に観察し得た1型糖尿病の1例

持続皮下インスリン注入療法（CSII）により妊娠・周産期・授乳期のインスリン必要量の推移を詳細に観察し得た1型糖尿病の1例

Insulin requirements throughout pregnancy in women with type 1 diabetes mellitus: three changes of direction

The aim of the study was to analyse the insulin requirements of women with type 1 diabetes mellitus throughout pregnancy. We have examined the weekly mean blood glucose (mmol/l), insulin requirements (U kg(-1) day(-1)) and total insulin requirements (U/day) in 65 women with type 1 diabetes mellitus and tight metabolic control since before pregnancy (HbA(1c) < or =6.0%). Both insulin requirement and total insulin requirement displayed a peak in week 9, a nadir in week 16 and a second peak in week 37. For the change in insulin requirement (4.08% per week) and in total insulin requirement (5.19% per week), the sharpest slope was observed from week 16 to week 37. However, two changes of direction took place in the first 11 weeks and eight out of nine episodes of severe hypoglycaemia requiring treatment with glucagon or i.v. glucose took place in the first 16 weeks. Pregnant women with type 1 diabetes mellitus and tight metabolic control since before pregnancy displayed changes in insulin requirement and total insulin requirement with successive changes of direction. The sharpest slope was observed between 16 and 37 weeks, but insulin requirements were more unstable in the first 16 weeks. This information could help patients and physicians to react to changes in glycaemic pattern in a prompt and adequate way.

Difference in Insulin Usage Patterns with Pubertal Development in Children with Type 1 Diabetes During Transition from Multiple Daily Injections to Continuous Subcutaneous Insulin Infusion (CSII) and Through the CSII Treatment

This study analyzed the changes in insulin requirement in the transition from multiple daily injections (MDI) to continuous subcutaneous insulin infusion (CSII) and the differences through the CSII treatment in pediatric patients in different pubertal developmental stages. We analyzed, through a longitudinal retrospective study, the insulin usage patterns and glycemic control of 40 patients with type 1 diabetes on CSII treatment for 12 months. The patients were subdivided in three groups: group A, 13 prepubertal subjects (Tanner stage I); group B, 15 pubertal subjects (Tanner stage II-IV); and group C, 12 postpubertal subjects (Tanner stage V). During the transition from MDI to CSII, the insulin requirements decreased significantly by 21 +/- 5% (0.89 +/- 0.26 U/kg/day vs. 0.70 +/- 0.11 U/kg/day). Through the CSII treatment the percentage of total daily insulin delivered as the basal rate in groups A, B, and C was 54-60%, 52-54%, and 52-54%, respectively. The number of basal rates per day was significantly higher in groups A and B. The overall profile of basal rate differed among the groups. During the night, prepubertal patients required more insulin from 12 p.m. to 2 a.m., whereas pubertal and postpubertal patients required more insulin between 2-3 a.m. to 7 a.m. Prepubertal patients had a maximum basal rate between 9 a.m. to 12 a.m. and 2 p.m. to 4 p.m., in contrast to pubertal and postpubertal patients between 2 p.m. to 3 p.m. and 5 p.m. to 6 p.m. The number of "extra" boluses per day was significantly higher in groups B and C compared to group A. Age-related differences exist in insulin usage patterns of pediatric patients on pump treatment. A greater knowledge of these variations may help to obtain optimum conditions in the CSII treatment in pediatric patients.

6627 Minimizing recurrence for desmoid tumours of the anterior abdominal wall: a five-years follow-up monocentric series

Insulin bolus calculators are simple decision support software tools incorporated in most commercially available insulin pumps and some capillary blood glucose meters. Although their clinical benefit has been demonstrated, their utilisation has not been widespread and their performance remains suboptimal, mainly because of their lack of flexibility and adaptability. One of the difficulties that people with diabetes, clinicians and carers face when using bolus calculators is having to set parameters and adjust them on a regular basis according to changes in insulin requirements. In this work, we propose a novel method that aims to automatically adjust the parameters of a bolus calculator. Periodic usage of a continuous glucose monitoring device is required for this purpose.To test the proposed method, an in silico evaluation under real-life conditions was carried out using the FDA-accepted Type 1 diabetes mellitus (T1DM) UVa/Padova simulator. Since the T1DM simulator does not incorporate intra-subject variability and uncertainty, a set of modifications were introduced to emulate them. Ten adult and ten adolescent virtual subjects were assessed over a 3-month scenario with realistic meal variability. The glycaemic metrics: mean blood glucose; percentage time in target; percentage time in hypoglycaemia; risk index, low blood glucose index; and blood glucose standard deviation, were employed for evaluation purposes. A t-test statistical analysis was carried out to evaluate the benefit of the presented algorithm against a bolus calculator without automatic adjustment.The proposed method statistically improved (p < 0.05) all glycemic metrics evaluating hypoglycaemia on both virtual cohorts: percentage time in hypoglycaemia (i.e. BG < 70 mg/dl) (adults: 2.7 ± 4.0 vs. 0.4 ± 0.7, p = 0.03; adolescents: 7.1 ± 7.4 vs. 1.3 ± 2.4, p = 0.02) and low blood glucose index (LBGI) (adults: 1.1 ± 1.3 vs. 0.3 ± 0.2, p = 0.002; adolescents: 2.0 ± 2.19 vs. 0.7 ± 1.4, p = 0.05). A statistically significant improvement was also observed on the blood glucose standard deviation (BG SD mg/dL) (adults: 33.5 ± 13.7 vs. 29.2 ± 8.3, p = 0.01; adolescents: 63.7 ± 22.7 vs. 44.9 ± 23.9, p = 0.01). Apart from a small increase in mean blood glucose on the adult cohort (129.9 ± 11.9 vs. 133.9 ± 11.6, p = 0.03), the rest of the evaluated metrics, despite showing an improvement trend, did not experience a statistically significant change.A novel method for automatically adjusting the parameters of a bolus calculator has the potential to improve glycemic control in T1DM diabetes management.

Altered insulin requirement in patients with type 1 diabetes and primary adrenal insufficiency receiving standard glucocorticoid replacement therapy

Current glucocorticoid replacement regimens fail to fully mimic physiologic cortisol secretion in patients with primary adrenal insufficiency. This may lead to changes in insulin requirement in patients with primary adrenal insufficiency and type 1 diabetes. Therefore, we assessed insulin requirement in patients with autoimmune polyendocrine syndrome type 2 (APS-2). Ten females with primary adrenal insufficiency and type 1 diabetes (mean duration of type 1 diabetes 13+/-11 years and of primary adrenal insufficiency 11+/-9 years) were retrospectively assessed regarding insulin regimen and insulin dose adjustment. Data were compared with control patients matched for age, sex and duration of diabetes drawn from all patients with type 1 diabetes attending the diabetes outpatient clinics at the University Hospital Wuerzburg for a scheduled consultation. Glycaemia was well controlled in both groups (mean HbA1c 6.99+/-0.81% in APS-2 patients versus 6.69+/-1.03% in control patients). The mean weight-adjusted daily dose of insulin was non-significantly higher in patients with APS-2 compared with control patients (0.69+/-0.35 IU/kg body weight versus 0.51+/-0.17 respectively). The mean insulin (IU)/carbohydrate-ratio for 10 g of carbohydrate in the morning was 1.9+/-1.0 and 1.4+/-0.5 respectively. However, the insulin/carbohydrate-ratios were significantly higher in the APS-2 patients both at noon (mean ratio 2.0+/-0.9 vs 1.1+/-0.5 in control patients) and in the evening (mean ratio 2.1+/-1.1 vs 1.3+/-0.5 respectively; P<0.05). Glucocorticoid replacement therapy in patients with primary adrenal insufficiency and type 1 diabetes leads to significant changes in insulin requirement compared with patients with type 1 diabetes only.

Dynamic Tight Glycemic Control During and After Cardiac Surgery Is Effective, Feasible, and Safe

Tight blood glucose control reduces mortality and morbidity in critically ill patients, but intraoperative glucose control during cardiac surgery is often difficult, and risks hypoglycemia. In this study, we evaluated the safety and efficacy of a nurse-driven insulin protocol (the Aalst Glycemia Insulin Protocol) for achieving a target glucose level of 80-110 mg/dL during cardiac surgery and in the intensive care unit (ICU). We included 483 nondiabetics and 168 diabetics scheduled for cardiac surgery with cardiopulmonary bypass. To anticipate rapid perioperative changes in insulin requirement and/or sensitivity during surgery, we developed a dynamic algorithm presented in tabular form, with rows representing blood glucose ranges and columns representing insulin dosages based on the patients' insulin sensitivity. The algorithm adjusts insulin dosage based on blood glucose level and the projected insulin sensitivity (e.g., reduced sensitivity during cardiopulmonary bypass and normalizing sensitivity after surgery). A total of 18,893 blood glucose measurements were made during and after surgery. During surgery, the mean glucose level in nondiabetic patients was within targeted levels except during (112 +/- 17 mg/dL) and after rewarming (113 +/- 19 mg/dL) on cardiopulmonary bypass. In diabetics, blood glucose was decreased from 121 +/- 40 mg/dL at anesthesia induction to 112 +/- 26 mg/dL at the end of surgery (P < 0.05), with 52.9% of patients achieving the target. In the ICU, the mean glucose level was within targeted range at all time points, except for diabetics upon ICU arrival (113 +/- 24 mg/dL). Of all blood glucose measurements (operating room and ICU), 68.0% were within the target, with 0.12% of measurements in nondiabetics and 0.18% in diabetics below 60 mg/dL. Hypoglycemia < 50 mg/dL was avoided in all but four (0.6%) patients (40 mg/dL was the lowest observed value). The Aalst Glycemia Insulin Protocol is effective for maintaining tight perioperative blood glucose control during cardiac surgery with minimal risk of hypoglycemia.

Insulin Aspart in Diabetic Pregnancy: State of the Art

Pregnancy in women with diabetes is associated with an increased risk of obstetric complications and perinatal mortality. Maintenance of near-normal glycemia during pregnancy can bring the prevalence of fetal, neonatal and maternal complications closer to that of the nondiabetic population. Changes in insulin requirements during pregnancy necessitate short-acting insulins for postprandial control of hyperglycemia. The fast-acting insulin analogue insulin aspart has been tested in a large, randomized trial of pregnant women with Type 1 diabetes and offers benefits in control of postprandial hyperglycemia with a tendency towards fewer episodes of severe hypoglycemia compared with human insulin. Treatment with insulin aspart was associated with a tendency toward fewer fetal losses and preterm deliveries than treatment with human insulin. Insulin aspart could not be detected in the fetal circulation and no increase in insulin antibodies was found. Thus, the use of insulin aspart in pregnancy is regarded safe.

Inhibition of GSK3 Promotes Replication and Survival of Pancreatic Beta Cells

Recent developments indicate that the regeneration of beta cell function and mass in patients with diabetes is possible. A regenerative approach may represent an alternative treatment option relative to current diabetes therapies that fail to provide optimal glycemic control. Here we report that the inactivation of GSK3 by small molecule inhibitors or RNA interference stimulates replication of INS-1E rat insulinoma cells. Specific and potent GSK3 inhibitors also alleviate the toxic effects of high concentrations of glucose and the saturated fatty acid palmitate on INS-1E cells. Furthermore, treatment of isolated rat islets with structurally diverse small molecule GSK3 inhibitors increases the rate beta cell replication by 2-3-fold relative to controls. We propose that GSK3 is a regulator of beta cell replication and survival. Moreover, our results suggest that specific inhibitors of GSK3 may have practical applications in beta cell regenerative therapies.

Increased subcutaneous insulin requirements in diabetic patients recently commenced on peritoneal dialysis

Diabetic patients often have reduced insulin requirements when they progress to renal failure. Since peritoneal dialysis (PD) solution contains glucose, the insulin requirement of these patients often increases after commenced on PD. However, the change in insulin requirement has not been studied systematically. We study 60 consecutive patients (32 male) with diabetic nephropathy newly started on PD. Their insulin requirement before and 6 months after initiation of dialysis is compared. Clinical factors affecting insulin requirement are explored. All patients received a standard 6 l/day dialysis exchange. The mean age was 60.3 +/- 8.9 years. Twelve patients did not require insulin before PD; four of them were started on insulin 6 months after dialysis. The average dosages of insulin 6 months before and after PD were 0.27 +/- 0.28 and 0.37 +/- 0.29 unit/kg/day, respectively (paired t-test, P < 0.001). The increment in dosage was 0.103 +/- 0.216 unit/kg/day. The dosage of insulin requirement correlates with the small solute transport of the peritoneal membrane, as represented by the mass transfer area coefficient (MTAC) of creatinine (r = -0.307, P = 0.017) and haemoglobin level (r = 0.284, P = 0.028), but not with body mass index (BMI). The change in insulin dosage correlates with the number of 2.5% dialysis cycle required per day (r = 0.433, P = 0.001), but not with peritoneal transport status or BMI. In patients who did not receive hypertonic exchange, the dosage of insulin increased by 1.5 +/- 11.1 unit/day. Each extra 2.5% 2 l exchange results in a 7.5 unit/day (95%CI 3.2-11.8, P = 0.001) increase in insulin requirement. Diabetic patients have a minimal increase in insulin requirement after initiation of PD per se, but the dosage of insulin increased markedly after exposure to hypertonic glucose solution. Our result provides a basis for the dosage adjustment of insulin in diabetic patients newly commenced on PD.

Implantable Insulin Pump Therapy: An Unusual Presentation of a Catheter-Related Complication

We report the case of a 63-year-old man who has a 19-year history of involvement in the implantable insulin pump program at Johns Hopkins University. After his most recent pump implantation in February 2004, his 24-h insulin requirement gradually increased from a baseline of 75 units to a peak of almost 500 units in June 2005. Surprisingly, insulin delivery from the pump and glycemic control remained satisfactory despite the dramatic change in insulin requirement. Laparotomy revealed a fibrous mass in the peritoneal cavity, with the track of the catheter extending into the mass. Insulin requirement declined post-resection of the mass and relocation of the catheter tip.

Changes in insulin requirement and glycemic control during pregnancy in women with type I diabetes

Changes in insulin requirement and glycemic control during pregnancy in women with type I diabetes

Effect of fat-free diet on insulin requirements in type I diabetes controlled with artificial beta-cell.

We investigated the effect of eliminating calories derived from fat sources on postprandial and basal insulin requirements in five patients with type I (insulin-dependent) diabetes mellitus. The patients were studied on a metabolic ward on two solid-food diets with similar quantities of carbohydrate and protein with or without the addition of fat. Diet A was isocaloric (weight maintenance) with calories distributed as 45% carbohydrate, 15% protein, and 40% fat. Diet B contained the same carbohydrate and protein content as diet A but was virtually fat free and therefore hypocaloric (1233 +/- 106 vs. 1830 +/- 99 cal, mean +/- SE). The diets were given as five equal meals each day on consecutive days. Insulin requirements and blood glucose measurements were determined by use of the artificial beta-cell. During the study, mean (+/- SE) preprandial blood glucose levels were maintained at 85 +/- 11 mg/dl, and peak postprandial blood glucose levels were less than 180 mg/dl. The elimination of fat calories had no effect on total (68.9 +/- 10.3 vs. 69.3 +/- 4.9 U/day), postprandial (9.8 +/- 3.8 vs. 10.3 +/- 3.7 U/meal), or basal (1.9 +/- 0.2 vs. 1.8 +/- 0.2 U/h) insulin requirements. Thus, despite a hypocaloric diet, no change in insulin requirements was noted when fat-derived calories were deleted from the diet. We conclude that fat-derived calories do not alter short-term basal or postprandial insulin requirements in type I diabetes.

Hormonal contraception in diabetic women: Acceptability and influence on diabetes control and ovarian function of a nonalkylated estrogen/progestogen compound

The clinical acceptability and the influence on diabetes control were investigated in 50 women with insulindependent diabetes mellitus (IDDM) during intake of a combined nonalkylated estrogen/progestogen compound (4 mg 17-β estradiol, 2 mg estriol and 1 mg norethindrone) for one year. In 6 IDDM women, the influence of the hormonal treatment on diabetes control and on ovarian function was investigated by measuring the concentration of glycosylated hemoglobin (Hb-Alc), fasting plasma glucose, serum estradiol, serum estrone, serum progesterone and sex hormone binding globulin (SHBG) capacity. No pregnancy occurred during the study and the overall continuation rate of 60% compare well with the continuation rate normally found in non-diabetic women after administration of conventional type oral contraceptives. No difficulties with diabetes control was registered and no significant changes in insulin requirements, 24-h urinary glucose excretion and Hb-Alc were found. Ovulation was inhibited during the hormonal intake as judged by serum progesterone measurements. Serum estroneincreased ( p < 0.05), but this had no influence on SHBG capacity, indicating that the estrogen/androgen balance was unchanged during treatment.

Management of the diabetic surgical patient. A systematic but flexible plan is the key.

Diabetes control is especially important when the patient is undergoing surgery, as the trauma can result in major metabolic changes. Complications of diabetes must be assessed preoperatively, since they themselves can lead to the need for surgery or can predispose to increased surgical or anesthetic risk. The preoperative blood glucose status of diabetics can be assessed by use of standard laboratory methods, self monitoring devices, urine glucose testing, or measurement of glycohemoglobin level. Blood glucose control can be maximized by designation of one physician on the health care team to be in charge of fluid, electrolyte, and insulin administration on perioperative days. This physician should follow a definite protocol of subcutaneous insulin administration guided by appropriate monitoring of blood glucose response. In special cases, such as surgery in the pregnant diabetic, a more complex scheme of management using low-dose insulin infusion may be required. Coexistence of another endocrine disease with diabetes should be recognized, since it may lead to otherwise unexpected changes in insulin requirements. A systematic and comprehensive yet flexible approach to the treatment of diabetes before, during, and after surgery puts a successful outcome well within the reach of the modern clinician.

Clinical trial of chromium and yeast supplements on carbohydrate and lipid metabolism in diabetic men

Chromium (Cr) deficiency in experimental animals and in humans sustained by prolonged total parenteral nutrition has been shown to cause diabetes mellitus. Prior trials in humans indicated that Cr supplements, in either inorganic or organic form, may improve carbohydrate utilization. We report here a clinical double-blind, random cross-over trial of inorganic chromium trichloride, a brewer's yeast that contained Cr as glucose-tolerance-factor (GTF), a brewer's yeast extract without GTF, and a placebo. Forty-three outpatient diabetic men received three of these supplements for 4 months each. Subgroups included 21 ketosis-prone, 7 ketosis-resistant non-obese, and 15 ketosis-resistant obese men. Cr levels were followed pre- and post-treatment in hair, red blood cells, plasma, and urine. Response of carbohydrate metabolism to treatment was assessed in terms of change in insulin requirements, fasting plasma glucose, plasma cholesterol, and triglycerides, as well as the change in plasma glucose, glucagon, and insulin or C-peptide levels in response to a standard meal. In some men, these parameters were also measured after iv tolbutamide. Both the inorganic and organic oral Cr supplements increased measurable body pools of Cr in hair and red blood cells by about 25%. However, fasting plasma glucose and lipids and the glucose response to either the standard meal or to tolbutamide were not significantly altered by any of the treatments.

Predicting insulin requirements for a portable insulin pump using the Biostator. Evidence for reversible insulin resistance in poorly controlled type I diabetics.

Glycemic control was achieved in 14 patients with insulin-dependent diabetes mellitus (IDDM) by 36-48-h treatment with a recently marketed clinical model, Biostator glucose controller (Life Science Instruments, Miles Laboratories, Elkhart, Indiana). Control was maintained by continuous subcutaneous insulin infusion with a portable pump, programmed using infusion profiles from the Biostator. Control of glycemic excursion with the Biostator was variable among patients. This control, reflected by the M-value or a blood glucose index (mean of pre-, peak, and 2-h postmeal levels for four meals) of each patient, correlated directly with their prior glycemic control, as assessed by hemoglobin A1c (HbA1c) level (r = 0.66, P less than 0.01 and r = 0.82, P less than 0.005, for M-value and blood glucose index, respectively). Total insulin infused by the Biostator/24 h overpredicted the subcutaneous infusion dose required on day 2 of pump treatment (183 +/- 11%, P less 0.001). Therefore, these data were not used to program the portable pump. Instead, total insulin dose was estimated using a dietary glucose/insulin (G/I) ratio. This ratio, derived from dietary total available glucose, urine glucose, and insulin dose/24 h during depot insulin treatment, accurately estimated total insulin for pump infusion (97 +/- 4%). The basal infusion rate of the Biostator between 2400 and 0600 h also exceeded the subcutaneous infusion requirement and was reduced to 40% for the initial pump basal rate. The remainder of the insulin (total minus basal) was distributed as premeal boluses according to the Biostator infusion profile for meals.(ABSTRACT TRUNCATED AT 250 WORDS)

Clofibrate in insulin-dependent diabetes.

Forty-four diabetic patients maintained on insulin entered a doubleblind crossover trial. They were given clofibrate 2 g daily for 6 weeks, either before or after a period of 6 weeks on placebo.Clofibrate did not cause any material change in insulin requirements and there was no change in body weight. Drug tolerance was good.The mean blood glucose was significantly lowered while taking clofibrate. Plasma fibrinogen and pre-beta-lipoprotein concentrations were also significantly decreased following clofibrate therapy.

EFFECT OF "FRACTIONATED" INSULINS ON TOTAL PLASMA INSULIN BINDING CAPACITY AND INSULIN REQUIREMENT IN SEVERE DIABETES

Serial observations of insulin requirement and total plasma insulin binding capacity have been carried out on six severe diabetics whose treatment was changed from standard soluble and isophane (NPH) insulins to "fractionated" preparations (Nordisk Insulin Ltd). No correlation was found between initial insulin dose and binding capacity, but changes in these two functions during the study period were closely correlated, both for the group as a whole and for individual patients in whom falls in insulin dose occurred. It is concluded that highly purified insulins could be valuable in the treatment of insulin-resistant cases, that their use is frequently associated with a gradual reduction in insulin dose, and that estimation of total plasma insulin binding capacity may indicate which patients are most likely to benefit from fractionated insulin. No sudden change in insulin requirement was seen on changing to purified insulin preparations.