Hypoglycemia secondary to insulinoma masking the onset of type 1 diabetes in an adolescent.
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ABSTRACT:
SUBMITTER: Subramani S
PROVIDER: S-EPMC8462061 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Differential diagnosis of hypoglycemia in the non-diabetic adult patient is complex and comprises various diseases, including endogenous hyperinsulinism caused by functional β-cell disorders. The latter is also designated as nesidioblastosis or non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS). Clinically, this rare disease presents with unspecific adrenergic and neuroglycopenic symptoms and is, therefore, often overlooked. A combination of careful clinical assessment, oral glucose tolerance testing, 72 h fasting, sectional and functional imaging, and invasive insulin measurements can lead to the correct diagnosis. Due to a lack of a pathophysiological understanding of the condition, conservative treatment options are limited and mostly ineffective. Therefore, nearly all patients currently undergo surgical resection of parts or the entire pancreas. Consequently, apart from faster diagnosis, more elaborate and less invasive treatment options are needed to relieve the patients from the dangerous and devastating symptoms. Based on a case of a 23-year-old man presenting with this disease in our department, we performed an extensive review of the medical literature dealing with this condition and herein presented a comprehensive discussion of this interesting disease, including all aspects from epidemiology to therapy.
| S-EPMC10296556 | biostudies-literature
Project description:BackgroundCognitive function among apparently healthy adolescents has been associated with cardiovascular morbidity and mortality. We examined the relationship between global and subdomain cognitive scores in adolescence and early-onset type 2 diabetes (T2D) in men and women.MethodsA nationwide, population-based study of 971,677 Israeli born adolescents (56% men; mean age 17.4 years) who were medically examined and their cognitive performance was assessed before compulsory military service during 1992-2010. Data included global and subdomain cognitive Z-scores (problem-solving, verbal abstraction and categorization, verbal comprehension, and mathematical abilities). Data were linked to the Israeli National Diabetes Registry. The relations between global and subdomain scores and incident T2D was determined using Cox proportional hazard models and logistic regression models. Analyses were conducted separately for men and women.FindingsDuring 16,095,122 person-years, 3,570 individuals developed T2D. After adjustment, those in the low compared to the high quintile of global cognitive Z-score had the highest risk for T2D; HR 2.46, (95% CI 2.10-2.88) for men and 2.33 (95% CI 1.88-2.89) for women. A one-unit lower global cognitive Z-score was associated with 1.41 (95% CI 1.34-1.48) and 1.46 (95% CI 1.36-1.56) increased risks for men and women, respectively. The relationship was noted for the cognitive subdomains scores as well as for the global cognitive score, with no heterogeneity across cognitive subdomains.InterpretationThis large nationally representative cohort suggests relationship between global, as well as subdomain cognitive scores in late adolescence, and incident early onset T2D in both sexes, which was independent of socioeconomic status.
| S-EPMC8479622 | biostudies-literature
Project description:Among nondiabetic individuals, mild glucose decrements alter brain activity in regions linked to reward, motivation, and executive control. Whether these effects differ in type 1 diabetes mellitus (T1DM) patients with and without hypoglycemia awareness remains unclear.Forty-two individuals (13 healthy control [HC] subjects, 16 T1DM individuals with hypoglycemia awareness [T1DM-Aware], and 13 T1DM individuals with hypoglycemia unawareness [T1DM-Unaware]) underwent blood oxygen level-dependent functional MRI brain imaging during a 2-step hyperinsulinemic euglycemic (90 mg/dl)-hypoglycemic (60 mg/dl) clamp for assessment of neural responses to mild hypoglycemia.Mild hypoglycemia in HC subjects altered activity in the caudate, insula, prefrontal cortex, and angular gyrus, whereas T1DM-Aware subjects showed no caudate and insula changes, but showed altered activation patterns in the prefrontal cortex and angular gyrus. Most strikingly, in direct contrast to HC and T1DM-Aware subjects, T1DM-Unaware subjects failed to show any hypoglycemia-induced changes in brain activity. These findings were also associated with blunted hormonal counterregulatory responses and hypoglycemia symptom scores during mild hypoglycemia.In T1DM, and in particular T1DM-Unaware patients, there is a progressive blunting of brain responses in cortico-striatal and fronto-parietal neurocircuits in response to mild-moderate hypoglycemia. These findings have implications for understanding why individuals with impaired hypoglycemia awareness fail to respond appropriately to falling blood glucose levels.This study was supported in part by NIH grants R01DK020495, P30 DK045735, K23DK109284, K08AA023545. The Yale Center for Clinical Investigation is supported by an NIH Clinical Translational Science Award (UL1 RR024139).
| S-EPMC5873861 | biostudies-other
Project description:The association of diabetes mellitus and insulinoma is unusual. We are reporting the case of a 58 years old patient having diabetes mellitus type 2 for several years. This patient was well balanced with oral anti-diabetic treatment. However, the diagnosis of insulinoma was discussed due to recent episodes of hypoglycemia that persisted even after stopping the treatment. Abdominal CT allowed the topographic diagnosis. The patient underwent a caudal pancreatectomy. Furthermore, the postoperative period shows that the diabetes mellitus requires the oral anti-diabetic treatment and basal insulin have to be stable. Then, the occurrence of hypoglycemia in the diabetic mellitus type 2 and, especially the persistence after discontinuation of therapy, suggest the unusual diagnosis of insulinoma as illustrated in our observation.
| S-EPMC5554613 | biostudies-other
Project description:The prevalence of both type 1 and type 2 diabetes among children and adolescents has been steadily increasing over the last few decades. However, as the general pediatric population becomes more obese and more ethnically diverse, reliance on phenotypic characteristics for distinguishing between these types of diabetes is becoming increasingly untenable. Yet, the recognition of differences in treatment strategies, associated disorders, and both short- and long-term diabetes and cardiovascular outcomes supports the importance of diagnostic efforts to make a distinction between diabetes types. An approach to determination of diabetes type is discussed, focused on the presence or absence of autoimmunity and assessment of ?-cell function. At the time of diagnosis, it is generally not possible to be certain of diabetes type, and therefore, initial treatment decisions must be made based on aspects of the presenting physiology, with adjustments in treatment approach made as the individual's course proceeds and additional information becomes available. The apparent overlap between type 1 and type 2 diabetes that occurs in obese adolescents has resulted in some controversy regarding mixed forms of diabetes that are ultimately semantic, but this does raise interesting questions about the treatment of type 1 diabetes in the presence of an insulin-resistant phenotype. Finally, the lack of information about the efficacy of treatment of cardiovascular risk factors, such as dyslipidemia and hypertension, along with the well-documented challenges in adherence to chronic illness treatment in this population, creates substantial challenges.
| S-EPMC2999981 | biostudies-other
Project description:Background and objectivesAmong people with diabetes mellitus, CKD may promote hypoglycemia through altered clearance of glucose-lowering medications, decreased kidney gluconeogenesis, and blunted counter-regulatory response. We conducted a prospective observational study of hypoglycemia among 105 individuals with type 2 diabetes treated with insulin or a sulfonylurea using continuous glucose monitors.Design, setting, participants & measurementsWe enrolled 81 participants with CKD, defined as eGFR<60 ml/min per 1.73 m2, and 24 control participants with eGFR?60 ml/min per 1.73 m2 frequency-matched on age, duration of diabetes, hemoglobin A1c, and glucose-lowering medications. Each participant wore a continuous glucose monitor for two 6-day periods. We examined rates of sustained level 1 hypoglycemia (<70 mg/dl) and level 2 hypoglycemia (<54 mg/dl) among participants with CKD. We then tested differences compared with control participants as well as a second control population (n=73) using Poisson and linear regression, adjusting for age, sex, and race.ResultsOver 890 total days of continuous glucose monitoring, participants with CKD were observed to have 255 episodes of level 1 hypoglycemia, of which 68 episodes reached level 2 hypoglycemia. Median rate of hypoglycemic episodes was 5.3 (interquartile range, 0.0-11.7) per 30 days and mean time spent in hypoglycemia was 28 (SD 37) minutes per day. Hemoglobin A1c and the glucose management indicator were the main clinical correlates of time in hypoglycemia (adjusted differences 6 [95% confidence interval, 2 to 10] and 13 [95% confidence interval, 7 to 20] fewer minutes per day per 1% higher hemoglobin A1c or glucose management indicator, respectively). Compared with control populations, participants with CKD were not observed to have significant differences in time in hypoglycemia (adjusted differences 4 [95% confidence interval, -12 to 20] and -12 [95% confidence interval, -29 to 5] minutes per day).ConclusionsAmong people with type 2 diabetes and moderate to severe CKD, hypoglycemia was common, particularly with tighter glycemic control, but not significantly different from groups with similar clinical characteristics and preserved eGFR.
| S-EPMC6556736 | biostudies-literature
Project description:The physiology of counterregulatory responses during hypoglycemia in intensively treated type 2 diabetic subjects is largely unknown. Therefore, the specific aims of the study tested the hypothesis that 1) 6 months of intensive therapy to lower A1C <7.0% would blunt autonomic nervous system (ANS) responses to hypoglycemia, and 2) antecedent hypoglycemia will result in counterregulatory failure during subsequent hypoglycemia in patients with suboptimal and good glycemic control.Fifteen type 2 diabetic patients (8 men/7 women) underwent 6-month combination therapy of metformin, glipizide XL, and acarbose to lower A1C to 6.7% and 2-day repeated hypoglycemic clamp studies before and after intensive therapy. A control group of eight nondiabetic subjects participated in a single 2-day repeated hypoglycemic clamp study.Six-month therapy reduced A1C from 10.2 +/- 0.5 to 6.7 +/- 0.3%. Rates of hypoglycemia increased to 3.2 episodes per patient/month by study end. Hypoglycemia (3.3 +/- 0.1 mmol/l) and insulinemia (1,722 +/- 198 pmol/l) were similar during all clamp studies. Intensive therapy reduced (P < 0.05) ANS and metabolic counterregulatory responses during hypoglycemia. Antecedent hypoglycemia produced widespread blunting (P < 0.05) of neuroendocrine, ANS, and metabolic counterregulatory responses during subsequent hypoglycemia before and after intensive therapy in type 2 diabetic patients and in nondiabetic control subjects.Intensive oral combination therapy and antecedent hypoglycemia both blunt physiological defenses against subsequent hypoglycemia in type 2 diabetes. Prior hypoglycemia of only 3.3 +/- 0.1 mmol/l can result in counterregulatory failure in type 2 diabetic patients with suboptimal control and can further impair physiological defenses against hypoglycemia in intensively treated type 2 diabetes.
| S-EPMC2646069 | biostudies-literature
Project description:Background and aimsAn association between hypoglycaemia and adverse cardiovascular events has been suggested from longitudinal and retrospective cohort studies. The complement pathway proteins in hypoglycemia are not well studied. Here, we hypothesized that these circulating proteins would be elevated in response to hypoglycemia in type 2 diabetes (T2D) through the inflammatory response.MethodsA prospective, parallel study in T2D (n = 23) and controls (n = 23). Subjects underwent insulin-induced hypoglycemia with blood sampling at baseline, hypoglycemia and post-hypoglycemia; SOMAscan proteomic analysis of complement pathway-related proteins, cytokines and inflammatory proteins was undertaken.ResultsAt baseline: Complement C2 (p < 0.05) and Factor B (p < 0.05) were elevated in T2D. At hypoglycemia: Complement C2 (p < 0.05) and Factor B (p < 0.01) remained elevated, whilst Factor I became elevated (p < 0.05) in T2D; Complement C4b became elevated in controls (p < 0.05). In the post-hypoglycemia follow up period, Complement C2, Factor B and Factor I remained elevated in T2D; in addition, Factor D, Factor H and mannose-binding protein C showed elevations in T2D, whilst properdin, complement C3b, Factor H-related protein 5, complement C1q and decay-accelerating factor (DAF) showed elevations in controls. Granger causality analysis showed that inflammatory proteins appeared to drive complement protein changes in T2D; conversely, in controls, complement proteins drove inflammatory protein changes.ConclusionsBaseline elevations in C2 and Factor B indicate upregulation of the complement pathway in T2D. Changes in complement pathway-related protein levels in response to hypoglycemia suggest both intrinsic and alternative pathway activation at 2-h that appears driven by the underlying inflammation in T2D and could contribute to a cardiovascular event.ClinicalTrials.gov NCT03102801. Date of registration April 6, 2017, retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT03102801?term=NCT03102801&draw=2&rank=1.
| S-EPMC9833243 | biostudies-literature
Project description:ObjectiveHypoglycemia is one of the major factors limiting implementation of tight glycemic control in patients with type 1 diabetes and is associated with increased morbidity and mortality during intensive insulin treatment. β-2 Adrenergic receptor (AR) agonists have been reported to diminish nocturnal hypoglycemia; however, whether long-acting inhaled β-2 AR agonists could potentially be used to treat or prevent hypoglycemia has not been established.Research design and methodsSeven patients with type 1 diabetes and seven healthy control subjects received inhaled formoterol (48 μg), a highly specific β-2 AR agonist, or a placebo during a hyperinsulinemic-hypoglycemic clamp study to evaluate its capacity to antagonize the effect of insulin. In a second set of studies, five subjects with type 1 diabetes received inhaled formoterol to assess its effect as a preventive therapy for insulin-induced hypoglycemia.ResultsDuring a hyperinsulinemic-hypoglycemic clamp, compared with placebo, inhaled formoterol decreased the glucose infusion rate required to maintain plasma glucose at a target level by 45-50% (P < 0.05). There was no significant effect on glucagon, epinephrine, cortisol, or growth hormone release (P = NS). Furthermore, in volunteers with type 1 diabetes 1 h after increasing basal insulin delivery twofold, glucose levels dropped to 58 ± 5 mg/dL, whereas hypoglycemia was prevented by inhaled formoterol (P < 0.001).ConclusionsInhalation of the β-2 AR-specific agonist formoterol may be useful in the prevention or treatment of acute hypoglycemia and thus may help patients with type 1 diabetes achieve optimal glucose control more safely.
| S-EPMC4542274 | biostudies-literature
Project description:BackgroundWe assessed in a nationwide cohort the association between adolescent BMI and early-onset (< 40 years) type 2 diabetes among Israelis of Ethiopian origin.MethodsNormoglycemic adolescents (range 16-20 years old), including 93,806 native Israelis (≥ 3rd generation in Israel) and 27,684 Israelis of Ethiopian origin, were medically assessed for military service between 1996 and 2011. Weight and height were measured. Data were linked to the Israeli National Diabetes Registry. Incident type 2 diabetes by December 31, 2016 was the outcome. Cox regression models stratified by sex and BMI categories were applied.Results226 (0.29%) men and 79 (0.18%) women developed diabetes during 992,980 and 530,814 person-years follow-up, respectively, at a mean age of 30.4 and 27.4 years, respectively. Among native Israeli men with normal and high (overweight and obese) BMI, diabetes incidence was 9.5 and 62.0 (per 105 person-years), respectively. The respective incidences were 46.9 and 112.3 among men of Ethiopian origin. After adjustment for sociodemographic confounders, the hazard ratios for type 2 diabetes among Ethiopian men with normal and high BMI were 3.4 (2.3-5.1) and 15.8 (8.3-30.3) respectively, compared to third-generation Israelis with normal BMI. When this analysis was limited to Israeli-born Ethiopian men, the hazard ratios were 4.4 (1.7-11.4) and 29.1 (12.9-70.6), respectively. Results persisted when immigrants of other white Caucasian origin were the reference; and among women with normal, but not high, BMI.ConclusionsEthiopian origin is a risk factor for early-onset type 2 diabetes among young men at any BMI, and may require selective interventions.
| S-EPMC7542395 | biostudies-literature