Hypokalemia and sudden cardiac death

Worldwide, approximately three million people suffer sudden cardiac death annually. These deaths often emerge from a complex interplay of substrates and triggers. Disturbed potassium homeostasis among heart cells is an example of such a trigger. Thus, hypokalemia and, also, more transient reductions in plasma potassium concentration are of importance. Hypokalemia is present in 7% to 17% of patients with cardiovascular disease. Furthermore, up to 20% of hospitalized patients and up to 40% of patients on diuretics suffer from hypokalemia. Importantly, inadequate management of hypokalemia was found in 24% of hospitalized patients. Hypokalemia is associated with increased risk of arrhythmia in patients with cardiovascular disease, as well as increased all-cause mortality, cardiovascular mortality and heart failure mortality by up to 10-fold. Long-term potassium homeostasis depends on renal potassium excretion. However, skeletal muscles play an important role in short-term potassium homeostasis, primarily because skeletal muscles contain the largest single pool of potassium in the body. Moreover, due to the large number of Na⁺/K⁺ pumps and K⁺ channels, the skeletal muscles possess a huge capacity for potassium exchange. In cardiovascular patients, hypokalemia is often caused by nonpotassium-sparing diuretics, insufficient potassium intake and a shift of potassium into stores by increased potassium uptake stimulated by catecholamines, beta-adrenoceptor agonists and insulin. Interestingly, drugs with a proven significant positive effect on mortality and morbidity rates in heart failure patients all increase plasma potassium concentration. Thus, it may prove beneficial to pay more attention to hypokalemia and to maintain plasma potassium levels in the upper normal range. The more at risk of fatal arrhythmia and sudden cardiac death a patient is, the more attention should be given to the potassium homeostasis.     

Treatment of diabetic ketoacidosis with subcutaneous insulin lispro: A review of the current evidence from clinical studies

AimLow-dose intravenous infusions of regular insulin, usually initiated in the emergency department and continued in the intensive care unit (ICU), are the standard care for patients with diabetic ketoacidosis (DKA) to ensure rapid resolution of hyperglycaemia and ketoacidosis. Several studies have evaluated whether subcutaneous injections of the rapid-acting analogue insulin lispro may be an alternative to intravenous insulin infusion for avoiding ICU admissions of uncomplicated DKA cases.MethodsThis review summarizes the current clinical evidence for the effectiveness and safety of subcutaneous insulin lispro injections in non-severe DKA patients. Relevant studies were identified by a systematic literature search through the PubMed database.ResultsTo date, four small randomized studies (156 patients overall; three studies in adults and one in paediatric patients with diabetes) have directly compared subcutaneous insulin lispro injections every 1–2 h vs continuous intravenous infusions of regular insulin. Patients with severe complications were excluded. In all studies, the mean time to resolution of DKA was similar in both treatment groups [range (three studies): lispro 10–14.8 h; regular insulin 11–13.2 h]. The mean time to resolution of hyperglycaemia, total insulin doses required, number of hospitalization days and number of hypoglycaemic episodes were similar in both treatment groups; no severe complications or DKA recurrences were reported, and one study showed a 39% cost reduction for the insulin lispro group.ConclusionIn patients with mild-to-moderate DKA, subcutaneous injections of insulin lispro every 1–2 h offer a feasible alternative to continuous intravenous infusions of regular insulin, and should now be evaluated in larger, more appropriately powered studies.     

Diabetic ketoacidosis: A consensus statement of the Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology and Pediatric Diabetoloy (SIEDP)

Background and aimDiabetic ketoacidosis (DKA) is a serious medical emergency once considered typical of type 1 diabetes (T1DM), but now reported to occur in type 2 and GDM patients as well. DKA can cause severe complications and even prove fatal. The aim of our study was to review recent international and national guidelines on diagnosis, clinical presentation and treatment of diabetic ketoacidosis, to provide practical clinical recommendations.Methods and resultsElectronic databases (MEDLINE (via PUB Med), Scopus, Cochrane library were searched for relevant literature. Most international and national guidelines indicate the same accurate flow chart to diagnose, to evaluate from clinical and laboratory point of view, and treat diabetic ketoacidosis.ConclusionPrompt diagnosis, rapid execution of laboratory analysis and correct treatment are imperative to reduce the mortality related to diabetic ketoacidosis. These recommendations are designed to help healthcare professionals reduce the frequency and burden of DKA.     

The UK case–control study of cerebral oedema complicating diabetic ketoacidosis in children

Aims/hypothesis Cerebral oedema complicating diabetic ketoacidosis (DKA) remains the major cause of morbidity and mortality in children with type 1 diabetes, but its aetiology remains unknown. Our objective was to determine the impact of baseline biochemical factors and of treatment-related variables on risk of the development of cerebral oedema in children with DKA.Materials and methods This was a national UK case–control study. Through the British Paediatric Surveillance Unit we identified 43 cases of cerebral oedema. Through a parallel reporting system, we also identified 2,940 episodes of DKA and selected 169 control subjects on the basis of comparable age, sex, numbers of new or known cases of diabetes and date of admission. Baseline biochemical data and treatment-related variables were extracted from the clinical notes of cases and control subjects.Results Allowing for differences in age, sex and new or known diabetes, cases were more acidotic at diagnosis of DKA (odds ratio [OR] for events in the least acidotic compared with the most acidotic tertile=0.02 [95% CI: 0.002–0.15], p<0.001). In addition, cases had higher potassium and urea levels at baseline. Calculated osmolality and baseline glucose were not significantly different. After allowing for severity of acidosis, insulin administration in the first hour (OR 12.7 [1.41–114.5], p=0.02) and volume of fluid administered over the first 4 h (OR 6.55 [1.38–30.97], p=0.01) were associated with risk. Low baseline plasma sodium and an elevated p_aCO₂ also contributed to risk in the final regression model. Bicarbonate administration was not associated with increased risk of an event when corrected for acidosis.Conclusions/interpretation In this case–control study of DKA, baseline acidosis and abnormalities of sodium, potassium and urea concentrations were important predictors of risk of cerebral oedema. Additional risk factors identified were early administration of insulin and high volumes of fluid. These observations should be taken into account when designing treatment protocols.     

Hypokalemic Paralysis Complicated by Concurrent Hyperthyroidism and Chronic Alcoholism: A Case Report

Thyrotoxic periodic paralysis (TPP) is characterized by the presence of muscle paralysis, hypokalemia, and hyperthyroidism. We report the case of a young man with paralysis of the lower extremities, severe hypokalemia, and concurrent hyperthyroidism. TPP was suspected; therefore, treatment consisting of judicious potassium (K⁺) repletion and β-blocker administration was initiated. However, urinary K⁺ excretion rate, as well as refractoriness to treatment, was inconsistent with TPP. Chronic alcoholism was considered as an alternative cause of hypokalemia, and serum K⁺ was restored through vigorous K⁺ repletion and the addition of K⁺-sparing diuretics.The presence of thyrotoxicosis and hypokalemia does not always indicate a diagnosis of TPP. Exclusion of TPP can be accomplished by immediate evaluation of urinary K⁺ excretion, acid-base status, and the amount of potassium chloride required to correct hypokalemia at presentation.     

Low‐density lipoprotein‐cholesterol lowering in individuals at intermediate cardiovascular risk: Percent reduction or target level?

Background

Recommendations for blood cholesterol management differ across different guidelines.

Hypothesis

Lipid‐lowering strategies based on low‐density lipoprotein‐cholesterol (LDL‐c) percent reduction or target concentration may have different effects on the expected cardiovascular benefit in intermediate‐risk individuals.

Methods

We selected individuals between 40 and 75 years of age with 10‐year risk for atherosclerotic cardiovascular disease (ASCVD) between 5.0% and <7.5% who underwent a routine health screening. For every subject, we simulated a strategy based on a 40% LDL‐c reduction (S_40%) and another strategy based on achieving LDL‐c target ≤100 mg/dL (S_target‐100). The cardiovascular benefit was estimated assuming a 22% relative risk reduction in major cardiovascular events for each 39 mg/dL of LDL‐c lowered.

Results

The study comprised 1756 individuals (94% men, 52 ± 5 years old). LDL‐c and predicted 10‐year ASCVD risk would be slightly lower in S_40% compared to S_target‐100. The number needed to treat to prevent 1 major cardiovascular event in 10 years (NNT₁₀) would be 56 with S_40% and 66 with S_target‐100. S_40% would prevent more events in individuals with lower baseline LDL‐c, whereas S_target‐100 would be more protective in those with higher LDL‐c. A dual‐target strategy (40% minimum LDL‐c reduction and achievement of LDL‐c ≤100 mg/dL) would be associated with outcomes similar to those expected with the S_40% (NNT₁₀ = 55).

Conclusions

In an intermediate‐risk population, cardiovascular benefit from LDL‐c lowering may be optimized by tailoring the treatment according to the baseline LDL‐c or by setting a dual‐target strategy (fixed dose statin plus achievement of target LDL‐c concentration).     

Do obese children with diabetic ketoacidosis have type 1 or type 2 diabetes?

ObjectiveMany obese children with unprovoked diabetic ketoacidosis (DKA) display clinical features of type 2 diabetes during follow up. We describe the clinical presentation, autoimmune markers and the long-term course of obese and lean children with DKA.Research design and methodsWe reviewed the medical records on the initial acute hospitalization and outpatient follow-up care of 21 newly diagnosed obese and 20 lean children with unprovoked DKA at Emory University affiliated children's hospitals between 1/2003 and 12/2006.ResultsObese children with DKA were older and predominantly male, had acanthosis nigricans, and had lower prevalence of autoantibodies to islet cells and glutamic acid decarboxylase than lean children. Half of the obese, but none of the lean children with DKA achieve near-normoglycemia remission and discontinued insulin therapy during follow-up. Time to achieve remission was 2.2 ± 2.3 months. There were no differences on clinical presentation between obese children who achieved near-normoglycemia remission versus those who did not. The addition of metformin to insulin therapy shortly after resolution of DKA resulted in lower hemoglobin A1c (HbA1c) levels, higher rates of near-normoglycemia remission, and lower frequency of DKA recurrence. Near-normoglycemia remission, however, was of short duration and the majority of obese patients required reinstitution of insulin treatment within 15 months of follow-up.ConclusionIn contrast to lean children with DKA, many obese children with unprovoked DKA display clinical and immunologic features of type 2 diabetes during follow-up. The addition of metformin to insulin therapy shortly after resolution of DKA improves glycemic control, facilitates achieving near-normoglycemia remission and prevents DKA recurrence in obese children with DKA.     

Incident Hyperkalemia,Hypokalemia, and Clinical Outcomes During Spironolactone Treatment of Heart Failure With Preserved Ejection Fraction: Analysis of the TOPCAT Trial

Background

In patients with heart failure and preserved ejection fraction (HF-PEF) randomized in the Americas as part of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, treatment with spironolactone enhanced the risk of hyperkalemia but reduced the risk of hypokalemia. We examined the clinical correlates and prognostic implications of incident hypo- and hyperkalemia during study follow-up.

Severe hypoglycemia and ketoacidosis over one year in Italian pediatric population with type 1 diabetes mellitus: A multicenter retrospective observational study

Background and aimsEvaluation of incidence and correlates of severe hypoglycemia (SH) and diabetes ketoacidosis (DKA) in children and adolescents with T1DM.Methods and resultsRetrospective study conducted in 29 diabetes centers from November 2011 to April 2012. The incidence of SH and DKA episodes and their correlates were assessed through a questionnaire administered to parents of patients aged 0–18 years. Incidence rates and incident rate ratios (IRRs) were estimated through multivariate Poisson regression analysis and multilevel analysis. Overall, 2025 patients were included (age 12.4 ± 3.8 years; 53% males; diabetes duration 5.6 ± 3.5 years; HbA1c 7.9 ± 1.1%). The incidence of SH and DKA were of 7.7 and 2.4 events/100 py, respectively. The risk of SH was higher in females (IRR = 1.44; 95%CI 1.04–1.99), in patients using rapid acting analogues as compared to regular insulin (IRR = 1.48; 95%CI 0.97–2.26) and lower for patients using long acting analogues as compared to NPH insulin (IRR = 0.40; 95%CI 0.19–0.85). No correlations were found between SH and HbA1c levels. The risk of DKA was higher in patients using rapid acting analogues (IRR = 4.25; 95%CI 1.01–17.86) and increased with insulin units needed (IRR = 7.66; 95%CI 2.83–20.74) and HbA1c levels (IRR = 1.63; 95%CI 1.36–1.95). Mother's age was inversely associated with the risk of both SH (IRR = 0.95; 95%CI 0.92–0.98) and DKA (IRR = 0.94; 95%CI 0.88–0.99). When accounting for center effect, the risk of SH associated with the use of rapid acting insulin analogues was attenuated (IRR = 1.48; 95%CI 0.97–2.26); 33% and 16% of the residual variance in SH and DKA risk was explained by center effect.ConclusionThe risk of SH and DKA is mainly associated with treatment modalities and strongly depends on the practice of specialist centers.     

The Molecular Genetics of Sulfonylurea Receptors in the Pathogenesis and Treatment of Insulin Secretory Disorders and Type 2 Diabetes

Sulfonylurea receptors (SURs) form an integral part of the ATP-sensitive potassium (K_ATP) channel complex that is present in most excitable cell types. K_ATP channels couple cellular metabolism to electrical activity and provide a wide range of cellular functions including stimulus secretion coupling in pancreatic β cells. K_ATP channels are composed of SURs and inward rectifier potassium channel (Kir6.x) subunits encoded by the ABCC8/9 and KCNJ8/11 genes, respectively. Recent advances in the genetics, molecular biology, and pharmacology of SURs have led to an increased understanding of these channels in the etiology and treatment of rare genetic insulin secretory disorders. Furthermore, common genetic variants in these genes are associated with an increased risk for type 2 diabetes. In this review we summarize the molecular biology, pharmacology, and physiology of SURs and K_ATP channels, highlighting recent advances in their genetics and understanding of rare insulin secretory disorders and susceptibility to type 2 diabetes.     

Management of diabetic ketoacidosis in a teaching hospital

Abstract The aim of our study was to evaluate clinical management of diabetic ketoacidosis (DKA) in a teaching hospital. We followed all the patients hospitalised for DKA over six years (1995–2000), and we recorded clinical data, laboratory finding at entrance and clinical management. We compared the data to the standards set in guidelines. Our study showed an important delay of initiation of intravenous fluid (70% of cases), an under-replacement with intravenous fluid (69% of cases) and with potassium therapy (80% of cases), and an excessive use of alkali therapy. In conclusion, suboptimal management of DKA occurred in a large percentage of patients.     

High- Versus Low-dose Losartan and Serum Potassium: An Analysis From HEAAL

BackgroundPatients with heart failure (HF) experience frequent alterations of serum potassium. Despite the high risk of events associated with hypokalemia, hyperkalemia is feared by clinicians and often leads to interruption or discontinuation of renin–angiotensin–aldosterone system inhibitors. Data on serum potassium of patients treated with different doses of renin–angiotensin–aldosterone system inhibitors are scarce.Methods and ResultsThe effects of high-dose vs low-dose losartan on clinical outcomes in patients with heart failure (HEAAL) trial randomized 3834 patients with HFrEF intolerant to angiotensin-converting enzyme inhibitors to losartan 150 mg/d (high dose) vs 50 mg/d (low dose). We studied the associations of serum potassium (baseline and time updated) with study outcomes and the effect of the randomized treatment on serum potassium. Patients with higher baseline potassium were older, had diabetes, poorer renal function, and used mineralocorticoid receptor antagonists more frequently. In time-updated models, hyperkalemia (>5.0 or ≥5.5 mmol/L) was not associated with cardiovascular death or the composite of cardiovascular death or HF hospitalization. Hypokalemia (serum potassium of ≤3.5 mmol/L, in particular) was associated with a higher risk of the composite of cardiovascular death or HF hospitalization (hazard ratio [HR] 1.58, 95% confidence interval [CI] 1.19–2.08), all-cause death (HR 1.68, 95% CI 1.26–2.24), and sudden cardiac death or resuscitated cardiac arrest (HR 1.74, 95% CI 1.11–2.73). High-dose losartan decreased the risk of hypokalemia (HR 0.77, 95% CI 0.63–0.92) and increased the risk of hyperkalemia (HR 1.21, 95% CI 1.05–1.39). High-dose losartan decreased the composite of cardiovascular death or HF hospitalizations consistently across the full spectrum of serum potassium at baseline (interaction P = .85).Conclusions: In patients with HF with reduced ejection fraction intolerant to angiotensin-converting enzyme inhibitors and treated with either high- or low-dose losartan, incident hypokalemia had a stronger association with poor outcomes than incident hyperkalemia. High-dose losartan reduced the incidence of hypokalemia, and its benefits were maintained across the full spectrum of serum potassium.     

Thyrotoxic periodic paralysis associated with lactic metabolic acidosis: Case report of an African man and review of literature

BackgroundThyrotoxic periodic paralysis (TPP) is a rare and most often acquired subtype of hypokalemic periodic paralysis. The association of varying degrees of muscle weakness, hyperthyroidism and hypokalemia characterizes it. The treatment requires potassium supplementation, control of hyperthyroidism and prevention measures. It is a frequent disease in Asian men, but much rare in Caucasian or African populations. This is the first report of TPP associated with lactic metabolic acidosis in an African man.Case presentationA 23 year-old African man, native from Morocco, with recurrent episodes of tetraparesis for eleven months, and abdominal pain, was referred for evaluation. Biochemical investigations showed severe hypokalemia associated with hyperthyroidism and lactic metabolic acidosis. His EKG showed signs of hypokalemia such as sinus tachycardia and U waves. After potassium supplementation, neurological recuperation was quick and complete. Thyroid ultrasound identified a hypoechogenic and hypervascularized goiter, associated with high levels of thyroid antibodies, in favor of Grave's disease. With antithyroid drugs and life-style changes, the patient did not have any other attack.Review of literatureIn addition to the case report, this article presents an extended review of literature, from the first large study reporting the diagnosis and incidence of TPP in 1957 to nowadays. Are reported here the latest information concerning epidemiology, clinical manifestations, complementary examinations, management and genetic finding. The lactic acidosis observed initially is exceptional, never described in TPP. TPP is a diagnostic and therapeutic emergency, requiring careful potassium supplementation, in order to avoid the risk of the onset of rebound hyperkalemia, to be maintained until the etiological treatment is effective. Paraclinical assessment with emergency EKG and electromyogram are essential to assess the impact.DiscussionIt is essential in the face of any hypokalaemic periodic paralysis, including in non-Asian subjects, to search hyperthyroidism.ConclusionsThis report demonstrates the importance of thyroid testing in case of acute muscle weakness, even in non-Asian patients in order to diagnose TPP. This is a rare but possible etiology, to be distinguished from the familial form of hypokalemic periodic paralysis. It also questions on the impact of TPP on energetic metabolism, in particular on lactic metabolism.     

Influence of potassium levels on one-year outcomes in elderly patients with acute heart failure

BackgroundAbnormal serum potassium levels (K⁺) in patients with heart failure (HF) relate to worse prognosis. We evaluated whether admission K⁺ levels predict 1-year outcomes in elderly patients admitted for acute HF.MethodsWe evaluated 2865 patients aged >74 years from the RICA Spanish Heart Failure Registry, classified according to admission serum K⁺ levels: hyperkalemia (>5.5 mmol/L), normokalemia (3.5–5.5 mmol/L) and hypokalemia (<3.5 mmol/L). We explored whether K⁺ levels were significantly associated with one-year all-cause mortality or hospital readmission and their combination.ResultsMean admission K⁺ value was 4.3 ± 0.6 mmol/L; 97 patients (3.38%) presented with hyperkalemia and 174 (6.06%) with hypokalemia. Overall, 43% of the patients died or were readmitted for HF during the follow-up period; the risk was higher for those with hyperkalemia (59% vs 41% in hypokalemic patients). The HR for one-year mortality was 1.43 (p = .073) and 1.67 for readmissions (p = .007) when K⁺ was >5.5 mmol/L and 1.08 (p = .618) and 0.90 (p = .533) respectively for K⁺ < 3.5 mmol/L. The HR for the combined outcome was 1.59 (1.19–2.13); p = .002 in hyperkalemic patients and 0.96 (0.75–1.23); p = .751in hypokalemic patients. Multivariate analysis showed a significant association of admission K⁺ values >5.5 mmol/L with the combined outcome of mortality and readmission (HR 1.15 [95% CI 1.04–1.27], p = .008).ConclusionIn patients hospitalized for decompensated HF, admission hyperkalemia predicts a higher mid-term risk for HF readmission and mortality, probably related to the significant higher risk of readmission.     

Profile of diabetic ketoacidosis at the National Diabetes and Endocrine Center in Tripoli,Libya, 2015

BackgroundDiabetic ketoacidosis (DKA) is a major acute metabolic complication of type I diabetes mellitus but may occur in type II diabetes during severe stressful conditions.AimThe aim of this study was to describe the clinical profile of DKA patients admitted to the National Diabetes and Endocrine Center in Tripoli, Libya, during 2015.Patients and methodsThe profiles of 490 patients admitted with DKA were retrospectively studied. All the data was collected from the patient files.ResultsMost of the patients (91.6%) were admitted to the intensive care unit. The mean age was 35.9 years. DKA was more common among young males with type I diabetes. The average duration of diabetes disease of the patient when admitted with DKA was 16.8 ± 8.2 years. The frequencies of patients admitted with mild, moderate or severe diabetic ketoacidosis were 49.8%, 32.7% and 17.8%, respectively. The most frequent causes of admission were insulin omission (21.8%), infection (20.2%), and wrong dose (11%). The cause of DKA was not known for 29.8% of the patients. DKA was more common among young males, and the rate increased with longer duration of the condition. Most of the patients (93.1%) were discharged in good health, and mortality was 0.6%.ConclusionMales and patients with a long duration of diabetes disease are more prone to develop DKA. The common causes of DKA were unknown in our study; however, admission of individuals with less serious illness, insulin omission, and infection may contribute to the development of DKA.     

Management of hyperkalemia in chronic heart failure using sodium zirconium cyclosilicate

BackgroundSodium zirconium cyclosilicate (SZC), a newly‐developed selective potassium binder, has been clinically available to treat hyperkalemia. SZC might be a promising option to manage hyperkalemia, particularly in patients with heart failure, who often require potassium‐sparing medications. However, the optimal initial dose of SZC therapy at a loading dose (30 g per day for the initial 2 days) versus a maintenance dose (5 g per day) remains unknown.MethodsConsecutive patients with heart failure and hyperkalemia who received 2‐day SZC therapy were retrospectively included. Safety and efficacy of SZC therapy were compared between the two strategies (maintenance versus loading).ResultsWe had 16 patients (76 years old, 11 men) who received 2‐day SZC therapy (4 maintenance dose group and 12 loading dose group). Serum potassium decreased 0.7 mEqL/L by 2‐day maintenance dose therapy and 1.3 mEq/L by 2‐day loading dose therapy. Following 2‐day SZC therapy, 25% of patients had hypokalemia, which was defined as serum potassium <4.0 mEq/L. Baseline lower serum potassium level was associated with the post‐SZC hypokalemia.ConclusionsSZC immediately decreases approximately 1.0 mEq/L of serum potassium in patients with heart failure and hyperkalemia. However, caution should be exercised when utilizing SZC at a loading dose specifically in those with mild hyperkalemia to prevent iatrogenic hypokalemia.     

Characterizing progressive beta-cell recovery after new-onset DKA in COVID-19 provoked A-β+ KPD (ketosis-prone diabetes): A prospective study from Eastern India

BackgroundRecent literature suggests a bi-directional relationship between COVID-19 infection and diabetes mellitus, with an increasing number of previously normoglycemic adults with COVID-19 being admitted with new-onset diabetic ketoacidosis (DKA). However, the possibility of COVID-19 being a potential trigger for A-β + ketosis-prone diabetes (KPD) in these patients needs elucidation. Our study aimed at analyzing such a cohort of patients and determining their natural course of β-cell recovery on serial follow-up.MethodsAfter initial screening, n = 42 previously non-diabetic patients with new-onset DKA and RT-PCR positive COVID-19, were included in our ten-month follow-up study. Of these, n = 22 were negative (suspected A-β + KPD) and n = 20 were positive (Type 1A DM) for autoantibodies (GAD/IA-2/ZnT8). Subsequently, n = 19 suspected KPD and n = 18 Type 1A DM patients were followed-up over ten months with serial assessments of clinical, biochemical and β-cell secretion. Amongst the former, n = 15 (79%) patients achieved insulin independence, while n = 4 (21%) continued to require insulin at ten-months follow-up.ResultsOn comparison, the suspected KPD patients showed significantly greater BMI, age, Hba1c, IL-6 and worse DKA parameters at presentation. Serial C-peptide estimations demonstrated significant β-cell recovery in KPD group, with complete recovery seen in the 15 patients who became insulin independent on follow-up. Younger age, lower BMI, initial severity of DKA and inflammation (IL-6 levels), along-with reduced 25-hydroxy-Vitamin-D levels were associated with poorer recovery of β-cell secretion at ten-month follow-up amongst the KPD patients,ConclusionsThis is the first prospective study to demonstrate progressive recovery of β-cell secretion in new-onset A-β + KPD provoked by COVID-19 infection in Indian adults, with a distinctly different profile from Type 1A DM. Given their significant potential for β-cell recovery, meticulous follow-up involving C-peptide estimations can help guide treatment and avoid injudicious use of insulin.     

Sintilimab induced diabetic ketoacidosis in a patient with small cell lung cancer: A case report and literature review

Rationale:Sintilimab is a novel programmed cell death receptor-1 (PD-1) inhibitor approved in the treatment of classical Hodgkin''s lymphoma and undergoing clinical trials for various malignancies. As a PD-1 inhibitor, sintilimab is known to cause autoimmune adverse events similar to other PD-1 inhibitors. Diabetic ketoacidosis (DKA) is a rare but severe adverse event of this therapy.Patient concerns:We report a case of a 59-year-old man who developed DKA after 5 doses of sintilimab for small cell lung cancer. His fasting glycemia level was 14.07 mmol/L, urine ketone bodies were 4+, arterial blood pH was 7.271, bicarbonate was 12.3 mmol/L, and glycated hemoglobin (HbA1c) was 7.4%. Extended investigations revealed that fasting C-peptide was undetectable (<0.003 nmol/L).Diagnosis:These laboratory investigations supported the diagnosis of fulminant type 1 diabetes mellitus, but no β-cell related antibodies were positive.Interventions:After remission of DKA, he was treated with insulin therapy to acquire a normalization of glycemia and the disappearance of symptoms.Outcomes:Sintilimab was withheld after 6 cycles and was converted to durvalumab to sustain the therapeutic effect.Lessons:This case and associated literature review illustrate the importance of educating and monitoring patients who start PD-1 inhibitor therapy regarding this potentially life-threatening complication.     

Life-threatening hypokalemia following rapid correction of respiratory acidosis

A 56-year-old woman with a history of paraplegia and chronic pain due to neuromyelitis optica (Devic's syndrome) was admitted to a spinal cord injury unit for management of a sacral decubitus ulcer. During the hospitalization, she required emergency transfer to the intensive care unit (ICU) because of progressive deterioration of respiratory muscle function, severe respiratory acidosis, obtundation and hypotension. Upon transfer to the ICU, arterial blood gas revealed severe acute-on-chronic respiratory acidosis (pH 7.00, PCO₂ 120 mm Hg, PO₂ 211 mm Hg). The patient was immediately intubated and mechanically ventilated. Intravenous fluid boluses of normal saline (10.5 L in about 24 h) and vasopressors were started with rapid correction of hypotension. In addition, she was given hydrocortisone. Within 40 min of initiation of mechanical ventilation, there was improvement in acute respiratory acidosis. Sixteen hours later, however, the patient developed life-threatening hypokalemia (K⁺ of 2.1 mEq/L) and hypomagnesemia (Mg of 1.4 mg/dL). Despite aggressive potassium supplementation, hypokalemia continued to worsen over the next several hours (K⁺ of 1.7 mEq/L). Urine studies revealed renal potassium wasting. We reason that the recalcitrant life-threatening hypokalemia was caused by several mechanisms including total body potassium depletion (chronic respiratory acidosis), a shift of potassium from the extracellular to intracellular space (rapid correction of respiratory acidosis with mechanical ventilation), increased sodium delivery to the distal nephron (normal saline resuscitation), hyperaldosteronism (secondary to hypotension plus administration of hydrocortisone) and hypomagnesemia. We conclude that rapid correction of respiratory acidosis, especially in the setting of hypotension, can lead to life-threatening hypokalemia. Serum potassium levels must be monitored closely in these patients, as failure to do so can lead to potentially lethal consequences.     

The association between GLP-1 receptor agonist and diabetic ketoacidosis in the FDA adverse event reporting system

Background and aimsIn 2019, the Medicines and Healthcare products Regulatory Agency (MHRA) of the United Kingdom (UK) and food and drug administration (FDA) of the United States of America (US) suggested that the relationship between glucagon-like peptide-1 receptor agonists (GLP-1RA) and diabetic ketoacidosis (DKA) deserved attention. This study is aiming to assess the association between GLP-1RA and DKA/ketosis in the FDA Adverse Event Reporting System (FAERS) database.Methods and resultsUsing FAERS database, we firstly extract the number of DKA reports from the first quarter (Q1) of 2004 to the fourth quarter (Q4) of 2019 and calculate proportional reporting ratios (PRRs). We then mined each FAERS file from 2004 Q1 to 2020 Q4 and obtained detailed information on DKA reports. From the first quarter (Q1) of 2004 to the fourth quarter (Q4) of 2019, there are 1382 DKA cases (1491 ketosis cases) associated with GLP-1RA in the FAERS database. There was a slight disproportionate reporting of DKA associated with overall GLP-1RA (PRR 1.49, 95%CI 1.24–1.79, p < 0.001) after excluding the impact of SGLT2i, T1D and insulin. Any disproportionality disappeared after selecting the GLP-1RA combined with insulin for comparison.ConclusionsWhen GLP-1RA not combined with insulin, the disproportionality of DKA reports associated with GLP-1RA was observed. Our analysis mined the FAERS database to provide evidence and highlight the potential association between DKA adverse events and GLP-1RA therapy that clinicians tend to overlook.