Finally,after 56 years of type 1 diabetes: a regimen that works

Prior to the availability of degludec and regular human insulin inhalation powder in the type 1 diabetic patient glycemic control with subcutaneous insulin injections was difficult to obtain due to nocturnal, pre-prandial and often severe hypoglycemia as well as post-prandial hyperglycemia and hypoglycemia due to ‘stacking’ of insulin. A 62-year-old female with type 1 diabetes for 56 years who could not be controlled with continuous subcutaneous insulin aspart infusion obtained glycemic control without significant hypoglycemia or increased post-prandial glycemic excursions utilizing degludec insulin for basal needs and technosphere before meals and between meals if needed. The availability of degludec and technosphere insulin improved the management of brittle type 1 diabetes.     

Hypothalamic‐pituitary‐adrenal axis activity in patients with active rheumatoid arthritis: a controlled study using insulin hypoglycemia stress test

Aim: To study the response of cortisol to insulin‐induced hypoglycemia in patients with active rheumatoid arthritis (RA). Methods: We measured the response of cortisol to insulin‐induced hypoglycemia (0.15 µ/kg) in 10 patients (6 female, 4 male) with active RA and 10 (6 female, 4 male) healthy controls. All patients had never received glucocorticoids before the study. The cortisol concentration was assessed by radioimmunoassay. Results: The mean age was 47.3 years (± 14.2 years) in patients and 43.5 years (± 10.6 years) in control subjects. The mean disease duration was 66.3 months (range 12–120). The basal serum levels of cortisol in patients with RA were not significantly different from those of controls. Although the mean serum cortisol levels after insulin‐induced hypoglycemia were lower in patients with RA than controls in all samples, the significant difference was seen only in the samples 60 min after insulin injection (18.59 vs. 24.28 µg/dL, P = 0.041). Conclusion: Our findings suggest that active RA is associated with dysfunction of the hypothalamic–pituitary‐adrenal axis.     

Hypoglycemia Worsened by Glucose Administration: A Case of Hypoglycemia Years After Gastric Surgery

BackgroundNoninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS) is a rare syndrome characterized by postprandial hypoglycemia with neuroglycopenic symptoms occurring 1 to 3 h after a meal. Diagnosis can be elusive, as the vast majority of patients have normal fasting blood glucose levels, and onset of hypoglycemic episodes can be a late complication of gastric surgery.Case ReportWe report the case of a 45-year-old woman presenting to the Emergency Department (ED) with new-onset seizures and hypoglycemia worsened by glucose administration. Surgical history is pertinent for a Roux-en-Y gastric bypass approximately 10 years prior to presentation.Why Should an Emergency Physician Be Aware of This?Although rare, it is important for emergency physicians to be vigilant of this disease process as a traditional treatment approach for hypoglycemia may be detrimental. Although cases of NIPHS have been documented in literature, its presence in emergency medicine-specific literature is seemingly nonexistent. Noninvasive imaging techniques will be normal, and diagnosis is dependent on awareness of this disease entity coupled with a detailed history.     

A general IGF-I overexpression effectively rescued somatic growth and bone deficiency in mice caused by growth hormone receptor knockout

Both growth hormone and insulin-like growth factor (IGF)-I are essential for postnatal somatic growth, while exerting distinct effects on energy homeostasis. Although growth hormone controls IGF-I production, whether IGF-I was the exclusive mediator of its growth promotion is still debated. In order to further explore their in vivo interactions in somatic growth as well as in energy homeostasis, we have crossed mutant (MT-IGF) transgenic mice onto the GHR ? / ? background. As expected, GHR gene deficiency caused growth retardation, including significant decreases in lumbar, femur and total body lengths, as well as decreased bone area, mineral content and mineral density. IGF-I overexpression alone in MT-IGF mice increased the weight, with no significant change in bone mineralization or longitudinal growth. Compared to GHR ? / ? littermates, overexpressed IGF-I in bitransgenic mice (GHR ? / ? and MT-IGF positive) exhibited fully restored body weight, lumbar (but not femur) and total body lengths, and normalized overall bone area, mineral content and density. On the other hand, there were significant changes in fasting glucose level, glucose tolerance, lean/fat masses and even adipose histology as a result of the transgenic/knockout double-crossing. IGF-I overexpression normalized glucose tolerance in GHR ? / ? mice. Intriguingly, on GHR+/ ? background of partial growth hormone insensitivity, overexpression of IGF-I caused a significant weight gain. Our results thus establish that the growth defect and bone deficiency caused by lack of growth hormone signaling can be effectively restored by increasing IGF-I production in vivo.     

Mutations in the Genes Encoding the Transcription Factors Hepatocyte Nuclear Factor 1 Alpha and 4 Alpha in Maturity‐Onset Diabetes of the Young and Hyperinsulinemic Hypoglycemia

Maturity‐onset diabetes of the young (MODY) is a monogenic disorder characterized by autosomal dominant inheritance of young‐onset (typically <25 years), noninsulin‐dependent diabetes due to defective insulin secretion. MODY is both clinically and genetically heterogeneous with mutations in at least 10 genes. Mutations in the HNF1A gene encoding hepatocyte nuclear factor‐1 alpha are the most common cause of MODY in most adult populations studied. The number of different pathogenic HNF1A mutations totals 414 in 1,247 families. Mutations in the HNF4A gene encoding hepatocyte nuclear factor‐4 alpha are a rarer cause of MODY with 103 different mutations reported in 173 families to date. Sensitivity to treatment with sulfonylurea tablets is a feature of both HNF1A and HNF4A mutations. The HNF4A MODY phenotype has been expanded by the reports of macrosomia in ～50% of babies, and more rarely, neonatal hyperinsulinemic hypoglycemia. The identification of an HNF1A or HNF4A gene mutation has important implications for clinical management in diabetes and pregnancy, but MODY is significantly underdiagnosed. Current research is focused on identifying biomarkers and developing probability models to identify those patients most likely to have MODY, until next generation sequencing technology enables cost‐effective gene analysis for all patients with young onset diabetes.     

A Project to Implement Use of 40% Dextrose Gel for Transient Neonatal Hypoglycemia

ObjectiveTo examine the effect of oral dextrose gel and oral feedings on newborns’ blood sugar homeostasis in the first day of life in an effort to decrease transfers to the NICU.DesignEvidence-based practice project.Setting/Local ProblemObstetric service at a large hospital in northeast Ohio with approximately 5,300 births annually. Neonates who experienced hypoglycemia were often transferred to the NICU for management if treatment measures failed, thereby increasing the cost of care and separating mothers from their newborns. During 2018, there were 54 neonates transferred to the NICU for hypoglycemia.ParticipantsPediatricians, neonatologists, neonatal nurse practitioners, clinical nurse specialists, managers, educators, and registered nurses.Intervention/MeasurementsAn interdisciplinary task force created a nurse-driven protocol and associated order set and also created and provided interdisciplinary education to all involved caregivers using a multimodal approach. Neonates’ charts were audited for the time period of April 2019 to April 2020 to evaluate participants’ compliance with the prescribed practice changes.ResultsThe number of neonates who qualified for blood glucose testing per the new protocol totaled 1,369. Of these, 188 (14%) met criteria for and were treated with 40% dextrose gel. Treatment with 40% dextrose gel was unsuccessful for 25 neonates, who were then transferred to the NICU. This is 29 fewer than were transferred in 2018.ConclusionThe use of oral dextrose gel and oral feedings was associated with a decrease in the number of newborns transferred to a higher level of care for treatment of hypoglycemia.     

Growth hormone secretion in diabetic retinopathy

Summary The plasma HGH response to insulin-induced hypoglycemia (0.2 U/kg) and the 24-h plasma HGH pattern during a normal day have been studied in 14 non obese long-term insulin-dependent diabetics with proliferative retinopathy, mean age 39 ± 2 (ranging between 24 and 50 years). Plasma glucose and FFA were also determined. The results were compared with those of 18 normal subjects of similar age and weight. The mean plasma HGH response to insulin in retinopathic diabetics was slightly lower (with no significant differences) than in controls in whom hypoglycemia was induced with a smaller dose of insulin (0.1 U/kg). This pattern of plasma HGH could be related to the delayed plasma glucose fall observed in retinopathic diabetics in comparison to normal subjects, even if the HGH peak after insulin in both groups (18.61 ± 4.32 ng/ml in retinopathic diabetics, 27.43 ± 4.19 in controls) did not seem to be correlated to the degree of hypoglycemia, but rather to the age of the subjects. Plasma HGH pattern, studied with blood samples taken every three hrs during a normal day, did not reveal differences between the diabetics and controls. Plasma glucose, however, was higher in retinopathic diabetics than in controls in spite of the insulin treatment. These results show that in diabetic patients with retinopathy, increased HGH secretion does not occur in conditions of ordinary life or after insulin-induced hypoglycemia, although the HGH plasma levels observed in retinopathic diabetics could be considered too high in relation to the elevated blood glucose levels. Traduzione a cura degli AA.     

Continuous Glucose Monitoring Versus Capillary Point-of-Care Testing for Inpatient Glycemic Control in Type 2 Diabetes Patients Hospitalized in the General Ward and Treated With a Basal Bolus Insulin Regimen

Background:

Continuous glucose monitoring (CGM) may improve the management of patients with type 2 diabetes hospitalized in the general ward by facilitating the detection of hyper- and hypoglycemic episodes. However, the lack of data on the accuracy and safety of CGM have limited its application.

Methods:

A prospective pilot study was conducted including 38 patients hospitalized in the general ward with a known diagnosis of type 2 diabetes mellitus (DM) and hyperglycemic individuals without a history of DM with a blood sugar of 140-400 mg on admission treated with a basal bolus insulin regimen. Inpatient glycemic control and the incidence of hypoglycemic episodes were compared between detection by CGM of interstitial fluid for up to 6 days and point-of-care (POC) capillary blood glucose monitoring performed pre- and postprandially, before bedtime and at 3 am.

Results:

No differences in average daily glucose levels were observed between CGM and POC (176.2 ± 33.9 vs 176.6 ± 33.7 mg/dl, P = .828). However, CGM detected a higher number of hypoglycemic episodes than POC (55 vs 12, P < .01). Glucose measurements were clinically valid, with 91.9% of patients falling within the Clarke error grid A and B zones.

Conclusions:

Our preliminary results indicate that the use of CGM in type 2 patients hospitalized in the general ward provides accurate estimation of blood sugar levels and is more effective than POC for the detection of hypoglycemic episodes and asymptomatic hypoglycemia.