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Cureus Aug 2021Globally, the prevalence of chronic, non-communicable diseases is increasing at an alarming rate. Amongst it, Type 2 diabetes mellitus (DM) is becoming more prevalent...
Globally, the prevalence of chronic, non-communicable diseases is increasing at an alarming rate. Amongst it, Type 2 diabetes mellitus (DM) is becoming more prevalent among young individuals due to obesity and sedentary habits. With the advent of COVID-19, there has been an increasing trend for diabetes and its complications. Here we describe a 13-year-old female girl with polyuria, polydipsia for two months with further assessment leading to a diagnosis of Type 2 DM who is now closely monitored by a pediatric endocrinologist. She remains euglycemic with insulin and lifestyle changes. Early-onset DM is complex and requires multidisciplinary care for preventing complications and comorbidities. Hence, early recognition and management are crucial.
PubMed: 34513530
DOI: 10.7759/cureus.17578 -
Cureus Aug 2021Diabetes mellitus (DM) is a metabolic syndrome that is spreading like an epidemic throughout the world without any differentiation of races and ethnic groups and has... (Review)
Review
Diabetes mellitus (DM) is a metabolic syndrome that is spreading like an epidemic throughout the world without any differentiation of races and ethnic groups and has become the cause of death worldwide. It is characterized by high levels of glucose in the blood and has different types classified on the basis of varying pathophysiology. Type 1 diabetes or insulin-dependent diabetes is characterized by insulin insufficiency due to autoimmune dysfunction. Type 2 diabetes or non-insulin-dependent diabetes results from the combination of resistance to insulin action or/and inadequate insulin secretion. Gestational diabetes (GDM) is defined as hyperglycemia due to insulin resistance during pregnancy. Other types include the monogenic type of DM such as neonatal diabetes mellitus (NDM), maturity-onset diabetes of young (MODY), and diabetes in metabolic syndrome. Diabetes is diagnosed by criteria given by American Diabetes Association (ADA) for different tests like fasting plasma glucose test and hemoglobin A1c test. It is characterized by polydipsia, polyphagia, hyperglycemia, and glucosuria. Diabetes mellitus is managed through medications but many studies have proven that consumption of particular foods leads to decreased glucose levels in diabetic patients. Seeds like sunflower and flax seeds have a role in the reduction of glucose levels and can be used to treat type 2 diabetes. The bioactive components in these seeds like chlorogenic acid in sunflower seeds and secoisolariciresinol diglucosoid are involved in the treatment of insulin resistance or insulin production. In different studies, different amounts of these seed extracts were consumed by rats and humans and it resulted in better glycemic control, which provides information that these seeds have anti-diabetic properties.
PubMed: 34540481
DOI: 10.7759/cureus.17256 -
Endocrinology, Diabetes & Metabolism... Dec 2019Durvalumab is a programmed cell death ligand 1 inhibitor, which is now approved in Australia for use in non-small-cell lung and urothelial cancers. Autoimmune diabetes...
SUMMARY
Durvalumab is a programmed cell death ligand 1 inhibitor, which is now approved in Australia for use in non-small-cell lung and urothelial cancers. Autoimmune diabetes is a rare immune-related adverse effect associated with the use of immune checkpoint inhibitor therapy. It is now being increasingly described reflecting the wider use of immune checkpoint inhibitor therapy. We report the case of a 49-year-old female who presented with polyuria, polydipsia and weight loss, 3 months following the commencement of durvalumab. On admission, she was in severe diabetic ketoacidosis with venous glucose: 20.1 mmol/L, pH: 7.14, bicarbonate 11.2 mmol/L and serum beta hydroxybutyrate: >8.0 mmol/L. She had no personal or family history of diabetes or autoimmune disease. Her HbA1c was 7.8% and her glutamic acid decarboxylase (GAD) antibodies were mildly elevated at 2.2 mU/L (reference range: <2 mU/L) with negative zinc transporter 8 (ZnT8) and islet cell (ICA) antibodies. Her fasting C-peptide was low at 86 pmol/L (reference range: 200-1200) with a corresponding serum glucose of 21.9 mmol/L. She was promptly stabilised with an insulin infusion in intensive care and discharged on basal bolus insulin. Durvalumab was recommenced once her glycaemic control had stabilised. Thyroid function tests at the time of admission were within normal limits with negative thyroid autoantibodies. Four weeks post discharge, repeat thyroid function tests revealed hypothyroidism, with an elevated thyroid-stimulating hormone (TSH) at 6.39 mIU/L (reference range: 0.40-4.80) and low free T4: 5.9 pmol/L (reference range: 8.0-16.0). These findings persisted with repeat testing despite an absence of clinical symptoms. Treatment with levothyroxine was commenced after excluding adrenal insufficiency (early morning cortisol: 339 nmol/L) and hypophysitis (normal pituitary on MRI).
LEARNING POINTS
Durvalumab use is rarely associated with fulminant autoimmune diabetes, presenting with severe DKA. Multiple endocrinopathies can co-exist with the use of a single immune checkpoint inhibitors; thus, patients should be regularly monitored. Regular blood glucose levels should be performed on routine pathology on all patients on immune checkpoint inhibitor. Clinician awareness of immunotherapy-related diabetes needs to increase in an attempt to detect hyperglycaemia early and prevent DKA.
PubMed: 31829972
DOI: 10.1530/EDM-19-0098 -
JCEM Case Reports Jan 2024Insulin edema is a poorly understood complication of insulin therapy. It has been reported in patients with both type 1 and 2 diabetes mellitus and typically occurs in...
Insulin edema is a poorly understood complication of insulin therapy. It has been reported in patients with both type 1 and 2 diabetes mellitus and typically occurs in patients with newly diagnosed or poorly controlled diabetes mellitus either after initiation or intensification of insulin therapy. A 20-year-old man presented with anorexia, polydipsia, and weight loss. Serum glucose on admission was 824 mg/dL (45.8 mmol/L) and hemoglobin A1c was >14.0. Additional workup was notable for positive anti-IA2 antibodies and low C-peptide of 0.5 ng/mL (1.1-4.4 ng/mL). He was diagnosed with type 1 diabetes mellitus and was started on insulin therapy with glargine and lispro. Within 4 days after insulin initiation, he developed bilateral leg swelling and reported a 25-pound (11.3-kg) weight gain over the next 10 days. After excluding other systemic causes of edema such as heart failure, renal failure, and liver failure, a diagnosis of insulin edema was made. Insulin glargine was switched to insulin degludec. Complete resolution of edema occurred within 3 days of switching the insulins. Insulin edema is a diagnosis of exclusion. Insulin's role in renal sodium handling, vasodilation, and increased vascular permeability have been postulated as possible mechanisms. Clinicians should be aware of this rare complication.
PubMed: 38116161
DOI: 10.1210/jcemcr/luad158 -
Clinical Kidney Journal Jan 2021The common finding of hypokalemic alkalosis in several unrelated disorders may confound the early diagnosis of salt-losing tubulopathy (SLT). Antenatal Bartter syndrome... (Review)
Review
The common finding of hypokalemic alkalosis in several unrelated disorders may confound the early diagnosis of salt-losing tubulopathy (SLT). Antenatal Bartter syndrome (BS) must be considered in idiopathic early-onset polyhydramnios. Fetal megabladder in BS may allow its distinction from third-trimester polyhydramnios that occurs in congenital chloride diarrhea (CCD). Fetal megacolon occurs in CCD while fecal chloride >90 mEq/L in infants is diagnostic. Failure-to-thrive, polydipsia and polyuria in early childhood are the hallmarks of classic BS. Unlike BS, there is low urinary chloride in hypokalemic alkalosis of intractable emesis and cystic fibrosis. Rarely, renal salt wasting may result from cystinosis, Dent disease, disorders of paracellular claudin-10b and Kir4.1 potassium-channel deficiency. Acquired BS may result from calcimimetic up-regulation of a calcium-sensing receptor or autoantibody inactivation of sodium chloride co-transporters in Sjögren syndrome. A relatively common event of heterozygous gene mutations for Gitelman syndrome increases the likelihood of its random occurrence in certain diseases of adult onset. Finally, diuretic abuse is the most common differential diagnosis of SLT. Unlike the persistent elevation in BS, urinary chloride concentration losses waxes and wanes on day-to-day assessment in patients with diuretic misuse.
PubMed: 33564404
DOI: 10.1093/ckj/sfaa172 -
American Journal of Physiology. Renal... May 2021The association between diabetes insipidus (DI) and chronic dietary K deprivation is well known, but it remains uncertain how the disorder develops and whether it is... (Comparative Study)
Comparative Study
The association between diabetes insipidus (DI) and chronic dietary K deprivation is well known, but it remains uncertain how the disorder develops and whether it is influenced by the sexual dimorphism in K handling. Here, we determined the plasma K (P) threshold for DI in male and female mice and ascertained if DI is initiated by polydipsia or by a central or nephrogenic defect. C57BL6J mice were randomized to a control diet or to graded reductions in dietary K for 8 days, and kidney function and transporters involved in water balance were characterized. We found that male and female mice develop polyuria and secondary polydipsia. Altered water balance coincided with a decrease in aquaporin-2 (AQP2) phosphorylation and apical localization despite increased levels of the vasopressin surrogate marker copeptin. No change in the protein abundance of urea transporter-A1 was observed. The Na-K-2Cl cotransporter decreased only in males. Desmopressin treatment failed to reverse water diuresis in K-restricted mice. These findings indicate that even a small fall in P is associated with nephrogenic DI (NDI), coincident with the development of altered AQP2 regulation, implicating low P as a causal trigger of NDI. We found that P decreased more in females, and, consequently, females were more prone to develop NDI. Together, these data indicate that AQP2 regulation is disrupted by a small decrease in P and that the response is influenced by sexual dimorphism in K handling. These findings provide new insights into the mechanisms linking water and K balances and support defining the disorder as "potassium-dependent NDI." This study shows that aquaporin-2 regulation is disrupted by a small fall in plasma potassium levels and the response is influenced by sexual dimorphism in renal potassium handling. The findings provided new insights into the mechanisms by which water balance is altered in dietary potassium deficiency and support defining the disorder as "potassium-dependent nephrogenic diabetes insipidus."
Topics: Animals; Antidiuretic Agents; Aquaporin 2; Deamino Arginine Vasopressin; Diabetes Insipidus, Nephrogenic; Disease Models, Animal; Drug Resistance; Female; Kidney; Male; Mice, Inbred C57BL; Phosphorylation; Potassium Deficiency; Potassium, Dietary; Risk Factors; Sex Characteristics; Water-Electrolyte Balance; Mice
PubMed: 33749322
DOI: 10.1152/ajprenal.00655.2020 -
International Journal of Preventive... 2021Diabetes mellitus (DM) is an endocrine disorder characterized by hyperglycemia, polyuria, polydipsia, and glucosuria. γ-aminobutyric acid (GABA) is an inhibitory... (Review)
Review
BACKGROUND
Diabetes mellitus (DM) is an endocrine disorder characterized by hyperglycemia, polyuria, polydipsia, and glucosuria. γ-aminobutyric acid (GABA) is an inhibitory neurotransmitter in the central nervous system (CNS) of humans and other mammals. GABA acts on two different receptors, which are GABA- and GABA-. Pancreatic β-cells synthesize GABA from glutamic acid by glutamic acid decarboxylase (GAD).
AIM
The objective of this study was to explore the potential role of pancreatic GABA on glycemic indices in DM.
METHODS
Evidence from experimental, preclinical, and clinical studies are evaluated for bidirectional relationships between pancreatic GABA and blood glucose disorders. A multiplicity of search strategies took on and assumed included electronic database searches of Medline and Pubmed using MeSH terms, keywords and title words during the search.
RESULTS
The pancreatic GABA signaling system has a role in the regulation of pancreatic hormone secretions, inhibition of immune response, improve β-cells survival, and change α cell into β-cell. Moreover, a GABA agonist improves the antidiabetic effects of metformin. In addition, benzodiazepine receptor agonists improve pancreatic β-cell functions through GABA dependent pathway or through modulation of pancreatic adenosine and glucagon-like peptide (GLP-1).
CONCLUSIONS
Pancreatic GABA improves islet cell function, glucose homeostasis, and autoimmunity in DM. Orally administered GABA is safe for humans, and acts on peripheral GABA receptors and represents a new therapeutic modality for both T1DM and T2DM. Besides, GABA- receptor agonist like benzodiazepines improves pancreatic β-cell function and insulin sensitivity through activation of GABA- receptors.
PubMed: 34084316
DOI: 10.4103/ijpvm.IJPVM_278_19 -
HCA Healthcare Journal of Medicine 2022Vitamin D derangements are a rare but important cause of hypercalcemia. Granulomatous disease is a primary cause of vitamin D derangements and is frequently associated...
INTRODUCTION
Vitamin D derangements are a rare but important cause of hypercalcemia. Granulomatous disease is a primary cause of vitamin D derangements and is frequently associated with sarcoidosis, tuberculosis, and in the present case, foreign body granulomatosis. Liquid or injectable silicone is used as a filler for cosmetic body contouring. Transgender patients may seek silicone injections as part of gender affirmation surgeries. Granuloma formation is a rare but well-described complication of injectable silicone.
CASE DESCRIPTION
A 40-year-old, assigned male at birth (AMAB) transgender female patient, with a history of HIV and chronic kidney disease (CKD) stage 3b, was admitted to the emergency department for evaluation of hypercalcemia. One year prior, the hypercalcemia was attributed to CKD secondary to HIV or HIV medications. The patient presented after two weeks of polyuria and polydipsia. Her vital signs were stable, and the physical exam, EKG, and chest x-ray were unremarkable. Labs were notable for calcium (14.1 mg/dL, assay normal range 8.5-10.5 mg/dL) and acute-on-chronic kidney disease. Follow-up labs were consistent with a vitamin D aberration causing hypercalcemia, raising suspicion for granulomatous disease. CT chest/abdomen/pelvis without contrast demonstrated diffuse skin thickening of the bilateral breasts and buttocks with associated ill-defined soft tissue density and scattered punctate calcifications. No hilar adenopathy or lung abnormalities were observed, decreasing the suspicion of sarcoidosis or an infectious etiology. The patient disclosed having received free silicone injections to which the hypercalcemia was attributed. After single doses of calcitonin (100U SC/IM) and zoledronic acid (4 mg IV), her hypercalcemia resolved. Kidney function gradually returned to baseline with IV fluids.
CONCLUSION
This case illustrates the importance of readily recognizing the imaging characteristics of free silicone granulomatosis, which showed subcutaneous fat infiltrated with soft tissue nodules and calcifications. The distribution of findings in the bilateral breast and buttocks and history of free silicone injections were most useful in arriving at a diagnosis and treatment plan.
PubMed: 37424606
DOI: 10.36518/2689-0216.1343 -
International Medical Case Reports... 2021Antiretroviral therapies prolong life expectancy and improve the quality of life of HIV-infected patients. Despite the documented benefits of antiretroviral drugs, its...
BACKGROUND
Antiretroviral therapies prolong life expectancy and improve the quality of life of HIV-infected patients. Despite the documented benefits of antiretroviral drugs, its use is not without side effects. Here, we report cases of new onset diabetes mellitus after taking a dolutegravir (DTG)-based ART regimen.
CASE PRESENTATION
HIV-infected patients who had been on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART regimens for more than a decade were shifted to integrase strand transfer inhibitors (dolutegravir)-based ART regimen as recommended by the National Comprehensive HIV Care Guideline. They were diagnosed to have diabetes mellitus with or without diabetic ketoacidosis (DKA) as evidenced by polyuria, polydipsia and fatigue, severe hyperglycemia (plasma glucose level >250 mg/dl) with or without ketonuria (3+) after 1-12 months of DTG-based ART regimen. Two of the patients who presented with DKA were treated with intravenous fluids and regular insulin. NPH insulin was started following recovery from DKA, which later shifted to metformin. One of the patients who presented with severe hyperglycemia without DKA was started with NPH insulin, which later shifted to metformin. Good glycemic control was obtained with metformin, while the DTG-based ART regimen was continued.
CONCLUSION
Hyperglycemia is a potential and noticed side effect of the DTG-based ART regimen. Baseline and periodic monitoring of plasma glucose might be required in ART regimens containing dolutegravir.
PubMed: 34349567
DOI: 10.2147/IMCRJ.S323233 -
Brain Sciences Dec 2022Cholinergic muscarinic stimulation of vast areas of the limbic brain induced a well-documented polydipsia in laboratory rats. This excessive water-drinking behavior has... (Review)
Review
Cholinergic muscarinic stimulation of vast areas of the limbic brain induced a well-documented polydipsia in laboratory rats. This excessive water-drinking behavior has not received any convincing biological and physiological interpretation for the last 50 years. This review offers such an interpretation and suggests that cholinergically induced drinking response, mostly by carbachol, is associated with activation of the ascending mesolimbic cholinergic system that serves for initiation of emotional aversive arousal of the organism. The ascending cholinergic system originates from the laterodorsal tegmental nucleus, has a diffuse nature, and affects numerous subcortical limbic structures. It is proposed that the carbachol-induced drinking response is related to the state of anxiety and does not serve the regulation of thirst. Instead, the response is anxiety-induced polydipsia that might occur as a soothing procedure that decreases the aversiveness of the negative emotional state induced by carbachol. It is concluded that carbachol-induced water-drinking behavior is a rewarding process that contributes to alleviating the feeling of anxiety by bringing some relief from the cholinergically induced aversive state, and it is a homologue to anxiety-driven polydipsia in humans.
PubMed: 36672042
DOI: 10.3390/brainsci13010060