Satisfactory Control Of Diabetes Research Articles

The impact of duration and control of type 1 diabetes mellitus on microvascular function is strongly modified by the gene for connexin 37

Abstract Introduction Type 1 diabetes mellitus (T1DM) is almost inevitably accompanied by microvascular dysfunction. This could be responsible for cardiovascular events and is supposed to be caused mainly by long-term exposure to hyperglycemia. Nevertheless, relationship between duration and control of T1DM with microvascular complications can be modified by genetic factors; one of frequently discussed candidate genes is connexin37 (cx37), namely its rs1764391 (C1019>T (Pro319>Ser) polymorphism. We already observed sex specific association between cx37 polymorphism with macrovascular changes but also with retinopathy, neuropathy and diabetic foot. In the recent study, we analyzed if the impact of duration and control of T1DM on directly measured microvascular function is modified by cx37 gene polymorphism. Methods In 235 men and 227 women with T1DM (mean age 43.6 ± 13.6 years; mean duration of diabetes 22.1 ± 11.3 years) wide spectrum of clinical, laboratory and hemodynamic parameters was measured. Establishment of microvascular function measured by photoplethysmography (detection of blood volume changes in the microvasculature in lower extremities) and calculated as Oliva/Roztocil index (ORI), was analyzed. Cx37 gene polymorphism was measured by PCR-RFLP. The correlation (Pearson’s correlation coefficient) between duration of T1DM and ORI was calculated including analysis of potential modification by control of diabetes (HbA1c) and by cx37 gene polymorphism and standardized for potential confounders (sex, age, smoking, presence of hypertension, central obesity …) by multiple regression. The analysis was conducted separately for duration of T1DM below (n=256) and above (n=206) 20 years as the linear relationship between ORI and T1DM duration tends to change accordingly. Results In patients with T1DM, distribution of Cx37 genotypes did not differ from the already described populations (TT/CT/CC: 9.7/44.4/45.9%). In patients with satisfactory control of diabetes (HbA1c<53 mmol/mol; n=105) we detected worsening (increase) of ORI with duration of diabetes only in TT homozygotes and CT heterozygotes for duration of at least 20 years (r=0.6, p=0.006), while in patients with unsatisfactory control (HbA1c>60 mmol/mol;n=270), we detected worsening of ORI with duration of diabetes only in CC homozygotes, both for duration 0-20 years (r=0.35, p=0.03) and for duration of at least 20 years (r=0.47, p=0.03). Conclusion Microvascular function in satisfactory controlled T1DM was worsening with diabetes duration only in T allele carriers of Cx37 gene, the worsening was detected only for patients with duration longer than 20 years. However, if T1DM control was insufficient, microcirculation was worsening only in CC homozygotes.

CARBOHYDRATE METABOLISM PARAMETERS IN CASE OF ADMINISTRATION OF ZINC-CONTAINING MEDICATIONS IN COMPLEX TREATMENT OF DIABETES MELLITUS

In order to improve treatment efficacy for patients with diabetes mellitus the possibility of administration of Zinkit (Woerwag Pharma, Germany) in a complex treatment program was studied. According to the results of a complex assessment of glycemia control indices in patients with diabetes mellitus 3 weeks after the enrollment to the study it was revealed, that additional to hypoglycemic therapy administration of zinc-containing medication not only promoted reliable decrease of fasting and 2-hours postprandial blood glucose level, but also approached glycemia indices to the goal levels of a satisfactory control of diabetes, provided significant reduction of HbA 1C level by 6,8 % of its initial level.

Personalized Medicine Switching from Insulin to Sulfonylurea in Permanent Neonatal Diabetes Mellitus Dictated by a Novel Activating ABCC8 Mutation

Neonatal diabetes mellitus (NDM) is a rare but important condition affecting approximately 1 in 100,000 newborns. Permanent form requires life-long treatment with difficulties in long-term compliance and metabolic complications. Exact genetic diagnosis can enable improved outcome and patient satisfaction by switching insulin injection to oral sulfonylureas. Successful cases have been reported with most experience on the KCNJ11-mutated permanent form. Here we report a successful experience in an ABCC8-mutated infant with permanent NDM. A 4-month-old Chinese girl was incidentally found to have hyperglycemia with baseline C-peptide of 0.05 nmol/L requiring insulin injection of 0.2 IU/kg/d. Genetic analysis of KCNJ11 and ABCC8 was performed by polymerase chain reaction and direct DNA sequencing at the age of 3 years. Sulfonylurea transition was conducted after the ABCC8 mutation detection. A novel homozygous ABCC8 NM_000352.3: c.3068 A>G; NP_000343.2: p.H1023R mutation was detected. C-peptide level increased to 0.14 nmol/L and HbA1c was normalized to 5.8% from 8.0% after 8 months of oral glibenclamide treatment with a maintenance dosage of 0.65 mg/kg/d. In this patient with ABCC8-mutated permanent NDM, oral sulfonylurea is also effective in achieving satisfactory diabetic control. Our study adds information to the personalized medicine practice of ABCC8-mutated permanent NDM.

The Continuous Glucose Monitoring System is Effective in Determining Major Factors Affecting Postprandial Glycemic Patterns in People with Type 2 Diabetes

We report a study intended to determine the time and magnitude of maximal postprandial glycemia in a cohort of subjects with type 2 diabetes. In an attempt to prevent the complications of type 2 diabetes, particular attention should be paid to controlling postprandial glycemia; the postprandial glucose peak induces oxidative stress and endothelial dysfunction, the first step toward accelerated atherogenesis.1 The contribution of postprandial glucose is predominant in patients with satisfactory control of diabetes, whereas the contribution of fasting glucose increases progressively with worsening diabetes.2 This is why postprandial hyperglycemia is often not recognized in patients with satisfactory levels of hemoglobin A1c (HbA1c). Furthermore, the type and composition of the meal affects the postprandial glycemic pattern. Thus, the peak of postprandial hyperglycemia is often overlooked. Continuous glucose monitoring was previously shown to be effective in detecting postprandial hyperglycemia in both type 1 and type 2 diabetics3,4 and to be helpful in determining food recommendations for diabetics.5 The aim of this study was to determine the main dietary factors influencing postprandial glycemia in typical type 2 diabetics, with the usage of a continuous glucose monitoring system CGMS® Systems Gold (Medtronic MiniMed, Northridge, CA), and to determine postprandial glycemic patterns following ingestion of meals of different composition. Eight, obese individuals (BMI 31–34 kg/m2) with type 2 diabetes, all treated with metformin, with good metabolic control, (HbA1c 140 mg/dl) was determined. An event was defined as a glucose value that persisted for at least 15 minutes. Table 1. The Clinical Characteristics of Study Participants High postprandial glucose values (>140 mg/dl, 0.5–4 h postprandial) were recorded after 38% of all meals. All episodes appeared after the meals rich in carbohydrates (carbohydrates >70% of calories) and rich in products with a high glycemic index (GI >70). The peak of glycemia appeared approximately 1 hour after ingestion of carbohydrate-rich meals, and approximately 3–4 hours after ingestion of protein/fat rich meals. In conclusion, postprandial glycemic excursions are relatively common in well-controlled, obese patients with type 2 diabetes who are treated with metformin. Glycemic load is one of the main factors affecting postprandial glycemia. The CGMS is effective in detecting postprandial hyperglycemia and determining the postprandial glycemia profiles following ingestion of meals of different composition, and thus may be helpful in establishing the dietary recommendations for people with diabetes.

Fetal growth patterns in fetuses of women with pregestational diabetes mellitus

To assess the effect of glucose control on the rate of growth of fetuses in women with pregestational diabetes mellitus (Types 1 and 2). All pregestational diabetic women booked at Mater Mothers' Hospital, Brisbane, Australia, between 1 January 1994 and 31 December 2002, were included. Pregnancies with congenital fetal anomalies, multiple pregnancies, and pregnancies terminated prior to 20 weeks' gestation were excluded. Dating scans were performed before 14 weeks' gestation and serial scans were performed at 18, 24, 28, 32 and 36 weeks. Fetal parameters, including biparietal diameter, femur length and abdominal circumference, were recorded. The daily growth rates for biparietal diameter, femur length, and fetal abdominal area were calculated and compared with those in a low-risk (non-diabetic) population. The growth rates in fetuses of women with satisfactory diabetic control (HbA1c < 6.5%) and unsatisfactory control (HbA1c > or = 6.5%) in the three trimesters were compared. A total of 174 diabetic pregnancies were included and a total of 997 ultrasound scans were performed. The growth rates for fetuses of mothers with diabetes mellitus were significantly higher than for those in the low-risk population. The z-scores for biparietal diameter, femur length, and fetal abdominal area were 0.18, 0.59 and 1.44, respectively. Fetuses of diabetic mothers with high HbA1c in the first trimester had significantly greater fetal abdominal area growth rate than those with normal HbA1c (fetal abdominal area z-score of 1.7 vs. 0.75, P = 0.009). Although the fetal abdominal area z-scores in fetuses of diabetic mothers with high HbA1c in the second or third trimesters were also higher than those with normal HbA1c levels, the differences did not reach statistical significance. Maternal obesity did not influence the fetal growth rate. The rate of growth of fetuses of diabetic mothers differs from that of the normal population. Growth acceleration persists until the late third trimester. Moreover, periconceptional glucose control appears to have a significant effect on accelerated growth of the fetal abdominal area.

Contribution of postprandial glucose to chronic hyperglycaemia: from the “glucose triad” to the trilogy of “sevens”

Even though fasting and postprandial glucose are both contributors to the overall hyperglycaemia as observed in patients with type 2 diabetes, their respective contributions are varying with the degree of diabetic control. The contribution of postprandial glucose is predominant in patients with satisfactory control of diabetes (HbAlc < 7.3%) whereas the contribution of fasting glucose increases progressively with worsening diabetes. As a consequence an overall picture of the diabetic control should normally be based on the assessment of the "glucose triad" with its three components: HbAlc which integrates the diabetic control over a 3-month period, fasting and postprandial glucose. The two later are good indicators of the glycaemic regulation over the two main physiological periods of daytime: the fasting and postprandial states. Postprandial glucose concentrations should be more particularly tested at mid-morning time since in most patients this period corresponds to the highest glucose concentrations of daytime. However postprandial measurements at 2-h after lunch provide an evaluation of the overall diabetic control since we have demonstrated that glucose concentrations < 7 mmol/L at this time point are excellent predictors of HbAlc levels < 7% (specificity 2 90%). Therefore, in order to simplify the work of health care providers the "glucose triad" concept can be translated into the trilogy of "sevens": HbA1c goals < 7% and postprandial glucose targets < 7 mmol/L 2-h after lunch, both for assessing a satisfactory diabetic control, and fasting glucose < 7 mmol/L for defining the non-diabetic state.

What should we measure in the diabetic patient and how does this respond to therapy?

Diabetes is characterized by hyperglycaemia and by the development of complications. The criteria for diagnosis have been revised and published by the World Health Organization (WHO). In a symptomatic patient, a random plasma glucose concentration of ≥11.1 mmol l−1 is diagnostic. For asymptomatic patients, two diagnostic tests are required. A fasting glucose level ≥7 mmol l−1 confirms the diagnosis (providing this is supported by a second diagnostic test). The 75 g oral glucose tolerance test, as recommended by the WHO, is used for diagnosis in borderline cases or for academic studies. A plasma glucose concentration ≥11.1 mmol l−1 at 2 h following oral glucose confirms the diagnosis (Table 1). Table 1 Values for diagnosis of diabetes mellitus and other categories of hyperglycaemia.

Driving and insulin--consensus, conflict or confusion?

All drivers requiring insulin treatment must be able to demonstrate satisfactory diabetic control and recognition of hypoglycaemic symptoms before being allowed to drive a motor vehicle. Clinicians have a duty to discuss fitness to drive with their patients. However, is the advice given consistent and in line with the regulations published by the Driver and Vehicle Licensing Authority (DVLA)? Six 'real-life' case scenarios were posted to clinicians (consultant diabetologists, specialist registrars and diabetes specialist nurses) within Wessex, UK. The identical cases were also sent to the DVLA for their comments. Sixty-six doctors (36 consultants) and 70 diabetes specialist nurses were contacted by postal questionnaire of which replies were received from 17 consultants (47%), 17 specialist registrars (57%) and 39 diabetes specialist nurses (56%). Although there was general agreement in cases of hypoglycaemia unawareness, there was disagreement where patients had or were at risk of unstable control albeit for a short time. Patients treated with insulin may receive conflicting information concerning their ability to drive.

Advances toward the implantable artificial pancreas for treatment of diabetes.

Recent research on development of the implantable artificial pancreas for treatment of diabetes is reviewed, based on a Medline literature search that focused on glucose sensors, insulin pumps, and pump control systems. To achieve a closed feedback loop, a clinically applicable implantable artificial pancreas requires miniaturization and coordination of three components: an insulin pump, a blood glucose monitor, and a control system. Recent clinical studies have demonstrated that implantable insulin pumps are feasible for satisfactory control of diabetes for over a year, with the major complication being obstruction of the infusion catheter. Research on continuous glucose sensors has predominantly used the glucose-oxidase reaction or near-infrared light spectroscopy. Implantable glucose oxidase sensors have been limited by local factors causing unstable signal output, whereas optical sensors must overcome interference by substances with absorption spectra similar to glucose. Investigators have developed control algorithms in an effort to stabilize operation of the integrated artificial pancreas in the face of variations in sensor output and pump function. The ultimate goals of fully automatic glucose control by an artificial pancreas include prevention or delay of chronic complications of diabetes, lowered risk of hypoglycemia, and less patient inconvenience and discomfort than with multiple daily glucose self-tests and insulin injection. The recent developments of optical glucose sensing, radiotelemetry systems to link pump and sensor, and miniaturization and refinement of insulin pumps are significant steps toward a clinically applicable artificial pancreas.

A case of insulin resistant diabetes with possible antibodies to insulin receptors.

A case of a 19-year-old, non-obese female with insulin resistant diabetes mellitus and polycystic ovary syndrome was reported. The maximal insulin requirement attained 360 units per day, but a satisfactory control of diabetes did not follow. The patient's serum contained not only anti-insulin antibodies, but also possible anti-insulin receptor antibodies which were demonstrated by the 125I-insulin binding test using insulin receptors derived from human placental plasma membrane. The insulin resistance in this case was assumed to be caused primarily by possible blocking antibodies to insulin receptors and partly by anti-insulin antibodies because of the following observations. First, high serum free insulin (165 microunits/ml) without hypoglycemia indicates the presence of insulin resistance due to other factors than antiinsulin antibodies. Second, the titer of 125I-insulin binding capacity of serum was not unusually higher than those seen in chronically insulin-treated diabetics. Third, immunologically heterospecies insulin (fish insulin) was also ineffective. The clinical features such as absence of ketoacidosis and association with polycystic ovary syndrome resemble those of an unique diabetic syndrome reported previously though acanthosis nigricans and endogenous hyperinsulinemia were not found in this case. Her insulin resistance remitted spontaneously and over the next 18 months' observation, her diabetes remained regulated without insulin therapy.

GROWTH IN DIABETIC CHILDREN: Studies in Identical Twins

An inquiry to determine whether early-onset diabetes leads to retardation of growth and development is described. Healthy monozygotic twins are normally very similar in height and therefore provide ideal comparisons for the effect of disease on height. The adult height and age of menarche in 35 young-onset identicaltwin pairs, one or both of whom has diabetes, have been studied. In all but one of 12 pairs in which one twin developed diabetes before puberty and the other did not, the affected twin was shorter; the mean difference was 21/4 in., which is much more than would be expected by chance. In the pairs in which diabetes appeared after puberty in one or both twins there was no significant difference in height. When both twins developed diabetes before puberty, again there was no significant difference in height. In 2 pairs of girl twins in whom diabetes appeared before puberty in one but not in the other, menarche was 4 and 5 years later in the affected than in the unaffected twin, whereas in the other pairs the difference was only about 1 month. These differences were seen despite apparently satisfactory diabetic control. It is concluded that diabetes of early onset leads to retardation of growth and development, even when its treatment is adequate as judged by conventional criteria, that these criteria are inadequate, and that the control of insulin-dependent diabetes is almost always poor.

Globin insulin: a clinical study

1. Six of ten patients required less globin than protamine for satisfactory diabetic control. The other four cases were regulated with the same dose of both types of insulin. 2. Of six patients stabilized with protamine and regular insulin, only two were able to secure similar regulation with globin insulin alone.