Clinical Diabetes and Endocrinology最新文献

Background: Genetic alterations and high levels of the vascular endothelial growth factor (VEGF) are presumptive risk factors for differentiated thyroid cancer (DTC).

Objective: This work aims to study the presence of - 634G/C polymorphism of vascular endothelial growth factor (rs2010963) and its' serum level in patients with DTC and comparing these results with those of the control subjects.

Material and method: The study was a retrograde case-control study that included seventy patients with DTCin addition to seventy apparently healthy control subjects. Blood sample was taken and subjected to study of - 634G/C VEGF polymorphism (rs2010963) by real time PCR and measurement of its' plasma level by immunoassay kit (ELISA).

Results: Regarding genotyping of VEGFA - 634G/C (rs2010963) polymorphism, there was significant increase in CG and GG genotypes (28.6%, 18.6% respectively) among patients compared to control subjects (20.0%, 4.3% respectively) and significant increase in CC genotype in control subjects (75.7%) compared to patients (52.9%), P = 0.001. The VEGF mean ± SD level was significantly elevated in patients compared to control subjects (1215.81 ± 225.78 versus 307.16 ± 91.81, P = 0.006). Moreover, there was significant increase in VEGF levels in patients with CG and GG genotypes (1295.9 ± 68.74, 1533.08 ± 109.95, respectively) compared to patients with CC genotype (1061 163.25), P = 0.001).

Conclusion: There was significant increase in GG and CG genotypes in patients with DTC compared to control subjects which may suggest a predisposing role for these genotypes in development of DTC. Moreover, there was significant increase in serum level of vascular endothelial growth factor in patients with GG and CG genotypes which may reflect the mechanism of these genotypes in development of DTC.

Background: Hypoglycemic syndrome is a potentially life-threatening condition that can lead to the disruption of brain and internal organ functions, and in severe cases to irreparable consequences or death. Factitious hypoglycemia (FH) is the deliberate use of insulin preparations or oral hypoglycemic drugs with the aim of lowering blood glucose levels into the pathologically-hypoglycemic range. Deliberate administration of insulin analogs may be difficult to prove because they might not have epitopes or containing low affinity epitopes that are the targets of antibodies used in particular assay kits.

Case presentation: A 34 years old woman was admitted to the Endocrinology Research Centre in September 2021 with a diagnosis of hypothyroidism and diabetes mellitus. Upon admission she complained of high glycemia indexes up to a maximum of 34 mmol/l ( 612 mg/dl), high TSH and low free T4 ( fT4) concentrations, despite reporting regular levothyroxine administration at a dose of 200 mcg per day. Under nursing supervision, her fT4 was rapidly normalized suggesting non-compliance as the cause of low thyroid hormone milieu. Glycemic fluctuations from 33 to 2.1 mmol/l (594 to 38 mg/dl) according to glucometer measurements were observed against the background of Lis-Pro insulin therapy, while no hyperglycemia was registered in venous blood and in the interstitial fluid concomitantly with the values found by glucometer. It was assumed that the patient's fingers were intentionally contaminated with glucose solution. Factitious hypo- and hyperglycemia were suspected. During yet another episode of hypoglycemia (1.86 mmol/L, 33 mg/dl) venous blood was drawn. Low to low-normal insulin and C-peptide values were found: 2.2 µU/ml (Roche kit) and 1.18 ng/ml, respectively. Therefore, insulin concentration in the same sample was re-tested with another kit (Abbott) and a significantly elevated value of 89.9 µU/ml was detected. Based on these results, FH was confirmed due to exogenous administration of an insulin analog undetectable by the Roche kit.

Conclusion: This clinical example illustrates to draw attention to multiple manipulations employed by subjects with Munchhausen Syndrome. In addition, this diagnosis may be further complicated by the laboratory use of immunoassay kits incapable of detecting some insulin analogs.

Background: Several systemic and sociodemographic factors have been associated with the development and progression of diabetic retinopathy (DR). However, there is limited investigation of the potential role sociodemographic factors may play in augmenting systemic risk factors of DR. We hypothesize that age, sex, race, ethnicity, income, and insurance payor have an impact on hemoglobin A1c (HbA1c), body mass index, and systolic blood pressure, and therefore an upstream effect on the development of DR and vision-threatening forms of DR (VTDR).

Methods: Multivariable analysis of longitudinal electronic health record data at a large academic retina clinic was performed. Sociodemographic factors included race, ethnicity, income, and insurance payor. Systemic risk factors for DR included hemoglobin A1c (HbA1c), systolic blood pressure (SBP), and body mass index (BMI). VTDR was identified from encounter diagnostic codes indicating proliferative retinopathy or diabetic macular edema. Patient-reported primary address zip codes were used to approximate income level, stratified into quartiles.

Results: From 2016 to 2018, 3,470 patients with diabetes totaled 11,437 visits were identified. Black patients had higher HbA1c and SBP compared to White patients. White patients had higher BMI and SBP compared to patients of unknown/other race and greater odds of VTDR than the latter. Patients of Hispanic ethnicity had significantly higher SBP than non-Hispanic patients. Low-income patients had higher BMI and SBP than high-income patients and greater odds of VTDR than the latter. Medicaid recipients had greater odds of VTDR than those with Blue Care Network (BCN) and Blue Cross Blue Shield (BCBS) insurance. Medicaid and Medicare recipients had higher SBP compared to BCBS recipients. Finally, both higher HbA1c and SBP had greater odds of VTDR. There were no differences in odds of VTDR between White and Black patients or between Hispanic and non-Hispanic patients.

Conclusion: Significant associations exist between certain sociodemographic factors and well-known risk factors for DR. Income and payor were associated with increased severity of systemic risk factors and presence of VTDR. These results warrant further investigation of how risk factor optimization and disease prevention may be further improved by targeted intervention of these modifiable sociodemographic factors.

Background: Insulin edema is a rare complication which can present after initiation or intensification of insulin therapy in people with diabetes. Initiation of closed-loop hybrid insulin pump therapy can result in rapid improvement in glycemic control for people with diabetes. We present a case in which transition to a closed-loop hybrid insulin pump system, followed by significant improvement in glycemic control, led to development of insulin edema in a person with type 1 diabetes.

Case presentation: We present a 51-year-old woman with type 1 diabetes of 16 years duration, on insulin pump therapy for more than 10 years, who presented for follow-up 7 weeks after transitioning to a hybrid closed-loop insulin pump system with continuous glucose monitoring (CGM). She complained of weight gain and bilateral lower extremity edema which had started two weeks after the change in pump modality. Laboratory studies and echocardiogram did not reveal any etiology of the acute edema. HbA1c was 3.3% lower than the previous measurement 15 weeks earlier, and there was a significant increase in the daily total insulin dose. With exclusion of other causes of acute edema, the patient was diagnosed with insulin edema and started on hydrochlorothiazide. On follow up, her lower extremity edema significantly improved although her weight did not return to baseline.

Conclusion: To our knowledge, this is the first case of insulin edema reported in a person with type 1 diabetes using CGM and a hybrid closed-loop insulin pump system. The increase in total daily insulin dose, rapid improvement of glycemic control, and lack of hypoglycemic episodes were important factors to consider in evaluation of this case. Use of hybrid closed-loop systems can help achieve rapid improvement in glycemic control in people with diabetes. This case suggests that consideration should be given to adjusting initial blood glucose targets when starting these remarkable new technologies in people with baseline poor glycemic control.

Background: Hyperinsulinemic hypoglycemia is the most common cause of severe and persistent hypoglycemia in neonates and children. It is a heterogeneous condition with dysregulated insulin secretion, which persists in the presence of low blood glucose levels.

Case presentation: We report a case of a 15 year-old male with hyperinsulinemic hypoglycemia, who underwent a subtotal pancreatectomy after inadequate response to medical therapy. Pathological examination was positive for nesidioblastosis (diffuse β-cell hyperplasia by H-E and immunohistochemical techniques). The patient's blood glucose levels normalized after surgery and he remains asymptomatic after 1 year of follow-up. The systematic review allowed us to identify 41 adolescents from a total of 205 cases reported in 22 manuscripts, from a total of 454 found in the original search done in PubMed and Lilacs.

Conclusions: Although very well reported in children, hyperinsulinemic hypoglycemia can occur in adolescents or young adults, as it happens in our reported case. These patients can be seen, treated and reported by pediatricians or adult teams either way due to the wide age range used to define adolescence. Most of them do not respond to medical treatment, and subtotal distal pancreatectomy has become the elected procedure with excellent long-term response in the vast majority.

Background: The prevalence of Gestational Diabetes Mellitus (GDM) varies worldwide among racial and ethnic groups, population characteristics (eg, average age and body mass index (BMI) of pregnant women), testing method, and diagnostic criteria. This study was aimed at determining the prevalence of GDM using the one-step 75-g Oral glucose tolerance test (OGTT) protocol, with plasma glucose measurement taken when patient is fasting and at 1 and 2 h and identify associated risk factors among pregnant women attending antenatal care clinic at St. Paul Hospital Millennium Medical College (SPHMMC) in Addis Ababa, Ethiopia.

Methods: Institution based cross sectional study was conducted from April, 2017 to October, 2017 at antenatal care clinic of SPHMMC among a randomly selected sample of 390 eligible pregnant women. Data were collected using a pretested questioner using 5% of the total sample size and later was modified accordingly to capture all the necessary data. Descriptive statistics, independent t-test and Binary Logistic Regression were used for analysis using SPSS version 23.0.

Results: The prevalence of GDM among the study population was 16.9%. Factors that affect prevalence of GDM were age group (AOR = 2.75, 95% CI: 1.03, 7.35 for 30-34 years old and AOR = 4.98, 95% CI: 1.703, 14.578 for ≥ 35 years old)and BMI (AOR = 2.23, 95% CI: 1.21, 4.11).

Conclusions: The prevalence of GDM among the study population is higher than previous reports in Ethiopia and even in other countries. This implies that these women and their newborns might be exposed to increased risk of immediate and long term complications from GDM including future risk of GDM and Type II Diabetes Mellitus.

Background: The increase in growth hormone (GH) secretion during a prolonged fast stimulates lipolytic rate, thereby augmenting the mobilization of endogenous energy at a time when fuel availability is very low.

Study aim: To identify the specific component of GH secretory pattern responsible for the stimulation of lipolytic rate during fasting in humans.

Study protocol: We measured lipolytic rate (using stable isotope dilution technique) after an overnight fast in 15 young, healthy, non-obese subjects (11 men and 4 women), and again on four separate occasions after a 59 h fast. These four prolonged fasting trials differed only by the contents of an infusion solution provided throughout the 59 h fasting period. Subjects were infused either with normal saline ("Control"; n = 15) or with graded doses of a GH Releasing Hormone Receptor Antagonist (GHRHa):10 μg/kg/h ("High"; n = 15), 1 μg /kg/h ("Medium"; n = 8), or 0.5 μg /kg/h ("Low"; n = 6).

Results: As expected, the 59 h fast completely suppressed plasma insulin levels and markedly increased endogenous GH concentrations (12 h vs 59 h Fast; p = 0.0044). Administration of GHRHa induced dose-dependent reduction in GH concentrations in response to the 59 h fast (p < 0.05). We found a strong correlation between the rate of lipolysis and GH mean peak amplitude (R = 0.471; p = 0.0019), and total GH pulse area under the curve (AUC) (R = 0.49; p = 0.0015), but not the GH peak frequency (R = 0.044; p = 0.8) or interpulse GH concentrations (R = 0.25; p = 0.115).

Conclusion: During prolonged fasting (i.e., 2-3 days), when insulin secretion is abolished, the pulsatile component of GH secretion becomes a key metabolic regulator of the increase in lipolytic rate.

Background: Individuals with multiple islet autoantibodies are at increased risk for clinical type 1 diabetes and may proceed gradually from stage to stage complicating the recruitment to secondary prevention studies. We evaluated multiple islet autoantibody positive subjects before randomisation for a clinical trial 1 month apart for beta-cell function, glucose metabolism and continuous glucose monitoring (CGM). We hypothesized that the number and type of islet autoantibodies in combination with different measures of glucose metabolism including fasting glucose, HbA1c, oral glucose tolerance test (OGTT), intra venous glucose tolerance test (IvGTT) and CGM allows for more precise staging of autoimmune type 1 diabetes than the number of islet autoantibodies alone.

Methods: Subjects (n = 57) at 2-50 years of age, positive for two or more islet autoantibodies were assessed by fasting plasma insulin, glucose, HbA1c as well as First Phase Insulin Response (FPIR) in IvGTT, followed 1 month later by OGTT, and 1 week of CGM (n = 24).

Results: Autoantibodies against GAD65 (GADA; n = 52), ZnT8 (ZnT8A; n = 40), IA-2 (IA-2A; n = 38) and insulin (IAA; n = 28) were present in 9 different combinations of 2-4 autoantibodies. Fasting glucose and HbA1c did not differ between the two visits. The estimate of the linear relationship between log2-transformed FPIR as the outcome and log2-transformed area under the OGTT glucose curve (AUC) as the predictor, adjusting for age and sex was - 1.88 (- 2.71, - 1.05) p = 3.49 × 10-5. The direction of the estimates for all glucose metabolism measures was positive except for FPIR, which was negative. FPIR was associated with higher blood glucose. Both the median and the spread of the CGM glucose data were significantly associated with higher glucose values based on OGTT, higher HbA1c, and lower FPIR. There was no association between glucose metabolism, autoantibody number and type except that there was an indication that the presence of at least one of ZnT8(Q/R/W) A was associated with a lower log2-transformed FPIR (- 0.80 (- 1.58, - 0.02), p = 0.046).

Conclusions: The sole use of two or more islet autoantibodies as inclusion criterion for Stage 1 diabetes in prevention trials is unsatisfactory. Staging type 1 diabetes needs to take the heterogeneity in beta-cell function and glucose metabolism into account.

Trial registration: ClinicalTrials.gov identifier: NCT02605148 , November 16, 2015.