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Endocrine Dec 2023Secondary diabetes mellitus (DM) in secretory pheochromocytomas and paragangliomas (PPGLs) is encountered in up to 50% of cases, with its presentation ranging from mild,... (Review)
Review
Secondary diabetes mellitus (DM) in secretory pheochromocytomas and paragangliomas (PPGLs) is encountered in up to 50% of cases, with its presentation ranging from mild, insulin resistant forms to profound insulin deficiency states, such as diabetic ketoacidosis and hyperglycemic hyperosmolar state. PPGLs represent hypermetabolic states, in which adrenaline and noradrenaline induce insulin resistance in target tissues characterized by aerobic glycolysis, excessive lipolysis, altered adipokine expression, subclinical inflammation, as well as enhanced gluconeogenesis and glucogenolysis. These effects are mediated both directly, upon adrenergic receptor stimulation, and indirectly, via increased glucagon secretion. Impaired insulin secretion is the principal pathogenetic mechanism of secondary DM in this setting; yet, this is relevant for tumors with adrenergic phenotype, arising from direct inhibitory actions in beta pancreatic cells and incretin effect impairment. In contrast, insulin secretion might be enhanced in tumors with noradrenergic phenotype. This dimorphic effect might correspond to two distinct glycemic phenotypes, with predominant insulin resistance and insulin deficiency respectively. Secondary DM improves substantially post-surgery, with up to 80% remission rate. The fact that surgical treatment of PPGLs restores insulin sensitivity and secretion at greater extent compared to alpha and beta blockade, implies the existence of further, non-adrenergic mechanisms, possibly involving other hormonal co-secretion by these tumors. DM management in PPGLs is scarcely studied. The efficacy and safety of newer anti-diabetic medications, such as glucagon-like peptide 1 receptor agonists and sodium glucose cotransporter 2 inhibitors (SGLT2is), as well as potential disease-modifying roles of metformin and SGLT2is warrant further investigation in future studies.
Topics: Humans; Insulin Resistance; Pheochromocytoma; Sodium-Glucose Transporter 2 Inhibitors; Insulin; Diabetic Ketoacidosis; Norepinephrine; Adrenal Gland Neoplasms; Diabetes Mellitus, Type 2
PubMed: 37731140
DOI: 10.1007/s12020-023-03492-7 -
Journal of Cardiovascular Development... Nov 2023Sodium-glucose cotransporter-2 (SGLT-2) inhibitors, also called gliflozins or flozins, are a class of drugs that have been increasingly used in the management of type 2... (Review)
Review
Sodium-glucose cotransporter-2 (SGLT-2) inhibitors, also called gliflozins or flozins, are a class of drugs that have been increasingly used in the management of type 2 diabetes mellitus (T2DM) due to their glucose-lowering, cardiovascular (CV), and renal positive effects. However, recent studies suggest that SGLT-2 inhibitors might also have a ketogenic effect, increasing ketone body production. While this can be beneficial for some patients, it may also result in several potential unfavorable effects, such as decreased bone mineral density, infections, and ketoacidosis, among others. Due to the intricate and multifaceted impact caused by SGLT-2 inhibitors, this initially anti-diabetic class of medications has been effectively used to treat both patients with chronic kidney disease (CKD) and those with heart failure (HF). Additionally, their therapeutic potential appears to extend beyond the currently investigated conditions. The objective of this review article is to present a thorough summary of the latest research on the mechanism of action of SGLT-2 inhibitors, their ketogenesis, and their potential synergy with the ketogenic diet for managing diabetes. The article particularly discusses the benefits and risks of combining SGLT-2 inhibitors with the ketogenic diet and their clinical applications and compares them with other anti-diabetic agents in terms of ketogenic effects. It also explores future directions regarding the ketogenic effects of SGLT-2 inhibitors.
PubMed: 37998523
DOI: 10.3390/jcdd10110465 -
Age and Ageing Jan 2024Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) reduce cardio-metabolic and renal outcomes in patients with type 2 diabetes (T2D) but their efficacy and safety in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) reduce cardio-metabolic and renal outcomes in patients with type 2 diabetes (T2D) but their efficacy and safety in older or frail individuals remains unclear.
METHODS
We searched PubMed, Scopus, Web of Science, Cochrane CENTRA and Google Scholar and selected randomised controlled trials and observational studies comparing SGLT2Is versus placebo/other glucose-lowering agent for people with frailty or older individuals (>65 years) with T2D and heart failure (HF). Extracted data on the change in HbA1c % and safety outcomes were pooled in a random-effects meta-analysis model.
RESULTS
We included data from 20 studies (22 reports; N = 77,083 patients). SGLT2Is did not significantly reduce HbA1c level (mean difference -0.13, 95%CI: -0.41 to 0.14). SGLT2Is were associated with a significant reduction in the risk of all-cause mortality (risk ratio (RR) 0.81, 95%CI: -0.69 to 0.95), cardiac death (RR 0.80, 95%CI: -0.94 to 0.69) and hospitalisation for heart failure (HHF) (RR 0.69, 95%CI: 0.59-0.81). However, SGLT2Is did not demonstrate significant effect in reducing in the risk of macrovascular events (acute coronary syndrome or cerebral vascular occlusion), renal progression/composite renal endpoint, acute kidney injury, worsening HF, atrial fibrillation or diabetic ketoacidosis.
CONCLUSIONS
In older or frail patients with T2D and HF, SGLT2Is are consistently linked with a decrease in total mortality and the overall burden of cardiovascular (CV) events, including HHF events and cardiac death, but not protective for macrovascular death or renal events. Adverse events were more difficult to quantify but the risk of diabetic ketoacidosis or acute kidney injury was not significantly increase.
Topics: Humans; Aged; Diabetes Mellitus, Type 2; Sodium-Glucose Transporter 2 Inhibitors; Glycated Hemoglobin; Diabetic Ketoacidosis; Sodium-Glucose Transporter 2; Frail Elderly; Heart Failure; Death; Glucose; Sodium
PubMed: 38287703
DOI: 10.1093/ageing/afad254 -
World Journal of Transplantation Sep 2023Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are novel oral hypoglycemic agents garnering much attention for their substantial benefits. These recent data have... (Review)
Review
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are novel oral hypoglycemic agents garnering much attention for their substantial benefits. These recent data have positioned SGLT2i at the forefront of diabetic chronic kidney disease (CKD) and heart failure management. SGLT2i use post-kidney transplant is an emerging area of research. Highlights from this mini review include the following: Empagliflozin is the most prescribed SGLT2i in kidney transplant recipients (KTRs), median time from transplant to initiation was 3 years (range: 0.88-9.6 years). Median baseline estimated glomerular filtration rate (eGFR) was 66.7 mL/min/1.73 m (range: 50.4-75.8). Median glycohemoglobin (HgbA1c) at initiation was 7.7% (range: 6.9-9.3). SGLT2i were demonstrated to be effective short-term impacting HgbA1c, eGFR, hemoglobin/hematocrit, serum uric acid, and serum magnesium levels. They are shown to be safe in KTRs with low rates of infections, hypoglycemia, euglycemic diabetic ketoacidosis, and stable tacrolimus levels. More data is needed to demonstrate long-term outcomes. SGLT2i appear to be safe, effective medications for select KTRs. Our present literature, though limited, is founded on precedent robust research in CKD patients with diabetes. Concurrent research/utilization of SGLT2i is vital to not only identify long-term patient, graft and cardiovascular outcomes of these agents, but also to augment management in KTRs.
PubMed: 37746038
DOI: 10.5500/wjt.v13.i5.239 -
The Western Journal of Emergency... Nov 2023Euglycemic diabetic ketoacidosis (DKA) (glucose <250 milligrams per deciliter (mg/dL) has increased in recognition since introduction of sodium-glucose co-transporter 2...
INTRODUCTION
Euglycemic diabetic ketoacidosis (DKA) (glucose <250 milligrams per deciliter (mg/dL) has increased in recognition since introduction of sodium-glucose co-transporter 2 (SGLT2) inhibitors but remains challenging to diagnose and manage without the hyperglycemia that is otherwise central to diagnosing DKA, and with increased risk for hypoglycemia with insulin use. Our objective was to compare key resource utilization and safety outcomes between patients with euglycemic and hyperglycemic DKA from the same period.
METHODS
This is a retrospective review of adult emergency department patients in DKA at an academic medical center. Patients were included if they were >18 years old, met criteria for DKA on initial laboratories (pH ≤7.30, serum bicarbonate ≤18 millimoles per liter [mmol/L], anion gap ≥10), and were managed via a standardized DKA order set. Patients were divided into euglycemic (<250 milligrams per deciliter [mg/dL]) vs hyperglycemic (≥250 mg/dL) cohorts by presenting glucose. We extracted and analyzed patient demographics, resource utilization, and safety outcomes. Etiologies of euglycemia were obtained by manual chart review. For comparisons between groups we used independent-group -tests for continuous variables and chi-squared tests for binary variables, with alpha 0.05.
RESULTS
We identified 629 patients with DKA: 44 euglycemic and 585 hyperglycemic. Euglycemic patients had milder DKA on presentation (higher pH and bicarbonate, lower anion gap; < 0.05) and lower initial glucose (195 vs 561 mg/dL, < 0.001) and potassium (4.3 vs 5.3 mmol/L, < 0.001). Etiologies of euglycemia were insulin use prior to arrival (57%), poor oral intake with baseline insulin use (29%), and SGLT2 inhibitor use (14%). Mean time on insulin infusion was shorter for those with euglycemic DKA: 13.5 vs 19.4 hours, = 0.003. Mean times to first bicarbonate >18 mmol/L and first long-acting insulin were similar. Incidence of hypoglycemia (<70 mg/dL) while on insulin infusion was significantly higher for those with euglycemic DKA (18.2 vs 4.8%, = 0.02); incidence of hypokalemia (<3.3 mmol/L) was 27.3 vs 19.1% ( = 0.23).
CONCLUSION
Compared to hyperglycemic DKA patients managed in the same protocolized fashion, euglycemic DKA patients were on insulin infusions 5.9 hours less, yet experienced hypoglycemia over three times more frequently. Future work can investigate treatment strategies for euglycemic DKA to minimize adverse events, especially iatrogenic hypoglycemia.
Topics: Adult; Humans; Adolescent; Diabetic Ketoacidosis; Bicarbonates; Insulin; Hypoglycemia; Glucose; Diabetes Mellitus
PubMed: 38165186
DOI: 10.5811/westjem.60361 -
Journal of Clinical & Translational... Dec 2023It has been suggested that there may be an association between type 1 diabetes (T1DM) and suicide, with one study reporting a rate 11 times that of the general... (Review)
Review
BACKGROUND
It has been suggested that there may be an association between type 1 diabetes (T1DM) and suicide, with one study reporting a rate 11 times that of the general population The aim of this paper was to investigate the association between Diabetic ketoacidosis (DKA: a life-threatening acute complication of T1DM) and suicidal behaviours in people with T1DM.
METHODS
We performed a search of the following databases: PubMed, PsychInfo, and Embase for papers which explored the association between suicidal behaviours and self-harm with DKA in T1DM. We excluded case reports and review papers.
RESULTS
Only three papers explored the relationship between DKA and self-harm. One study found an association between DKA and self-harm in a national cohort of people with type 1 diabetes and schizophrenia. The second found a significant increase in psychiatric admissions for self-harm following an episode of DKA. The third study reported that patients with diabetes and a history of self-harm were at elevated risk of a range of diabetes complications including DKA. These findings indicate an association between DKA and self-harm and support the guidelines in recommending a psychosocial assessment where DKA cannot be explained.
CONCLUSIONS
This review suggests that DKA is associated with suicidal or self-injurious behaviours. The small number of studies and the seriousness of this issue highlight the importance of further research on this topic, to improve the evidence base for the identification and treatment of risk of suicidal behaviours in people with T1DM.
PubMed: 37840692
DOI: 10.1016/j.jcte.2023.100325 -
Pediatric Health, Medicine and... 2023The coronavirus disease (COVID-19) pandemic affected the management and follow-up of several chronic ailments, including pediatric type 1 diabetes mellitus (T1DM).... (Review)
Review
The coronavirus disease (COVID-19) pandemic affected the management and follow-up of several chronic ailments, including pediatric type 1 diabetes mellitus (T1DM). Restricted access to healthcare and fear of contracting the virus during medical facility visits resulted in poor compliance, irregular follow-up visits, treatment, and delayed diagnosis of complications in pediatric diabetes such as diabetic ketoacidosis (DKA). As such, the incidence of complicated DKA in resource-limited settings is high due to delayed presentation, poor compliance with therapy, and associated comorbidities such as malnutrition and sepsis. The pandemic had only added to the woes. The increased surge in DKA, in the face of limited resources, prompted clinicians to find alternative solutions to manage these children effectively. In this narrative review, we discuss the key challenges faced globally while caring for children with T1DM and DKA during the COVID-19 pandemic, and the lessons learned thereof.
PubMed: 37691882
DOI: 10.2147/PHMT.S384104 -
International Journal of Endocrinology... Jul 2023Despite evidence about the relationship between diabetic ketoacidosis (DKA) and infectious diseases, our knowledge of DKA during the coronavirus disease 2019 (COVID-19)...
BACKGROUND
Despite evidence about the relationship between diabetic ketoacidosis (DKA) and infectious diseases, our knowledge of DKA during the coronavirus disease 2019 (COVID-19) pandemic remains unclear.
OBJECTIVES
This study aimed to compare the DKA situation among individuals with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) during the COVID-19 pandemic compared to pre-pandemic.
METHODS
This retrospective-longitudinal study included individuals with T1DM and T2DM hospitalized with newly diagnosed DKA before (March to August 2018 and 2019) and during (March to August 2020 and 2021) the COVID-19 pandemic. Demographics, the frequency of new-onset diabetes mellitus (DM) and new-onset DKA, days of hospitalization, DKA severity, laboratory tests, and mortality were assessed.
RESULTS
Of 162 patients with DKA, 139 patients were newly diagnosed. The frequency of individuals with new-onset DM had increased during the pandemic compared to pre-pandemic (P = 0.047). Moreover, new-onset DKA was higher in 2020 and 2021 versus 2019 and 2018 (P = 0.002). Significantly, there were no T2DM patients with DKA in pre-pandemic, but DKA admissions in people with T2DM increased in 2021 (P < 0.001). The severity of new-onset DKA had increased during the pandemic compared to pre-pandemic (P = 0.000). However, there was no significant difference between pre-and the pandemic regarding mortality (P = 0.981). Additionally, hospitalization length (P = 0.043) and mortality (P = 0.038) were higher in patients with T2DM compared to T1DM.
CONCLUSIONS
During the COVID-19 pandemic, the frequency of DKA and its severity was higher than in pre-pandemic, and COVID-19 can be more life-threatening in patients with T2DM. Therefore, healthcare providers should be alert to DKA, especially in patients with T2DM.
PubMed: 38028247
DOI: 10.5812/ijem-134882