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Open access

Suguru Watanabe, Jun Kido, Mika Ogata, Kimitoshi Nakamura and Tomoyuki Mizukami

Summary

Hyperglycemic hyperosmolar state (HHS) and diabetic ketoacidosis (DKA) are the most severe acute complications of diabetes mellitus (DM). HHS is characterized by severe hyperglycemia and hyperosmolality without significant ketosis and acidosis. A 14-year-old Japanese boy presented at the emergency room with lethargy, polyuria and polydipsia. He belonged to a baseball club team and habitually drank sugar-rich beverages daily. Three weeks earlier, he suffered from lassitude and developed polyuria and polydipsia 1 week later. He had been drinking more sugar-rich isotonic sports drinks (approximately 1000–1500 mL/day) than usual (approximately 500 mL/day). He presented with HHS (hyperglycemia (1010 mg/dL, HbA1c 12.3%) and mild hyperosmolality (313 mOsm/kg)) without acidosis (pH 7.360), severe ketosis (589 μmol/L) and ketonuria. He presented HHS in type 1 diabetes mellitus (T1DM) with elevated glutamate decarboxylase antibody and islet antigen 2 antibody. Consuming beverages with high sugar concentrations caused hyperglycemia and further exacerbates thirst, resulting in further beverage consumption. Although he recovered from HHS following intensive transfusion and insulin treatment, he was significantly sensitive to insulin therapy. Even the appropriate amount of insulin may result in dramatically decreasing blood sugar levels in patients with T1DM. We should therefore suspect T1DM in patients with HHS but not those with obesity. Moreover, age, clinical history and body type are helpful for identifying T1DM and HHS. Specifically, drinking an excess of beverages rich in sugars represents a risk of HHS in juvenile/adolescent T1DM patients.

Learning points:

  • Hyperglycemic hyperosmolar state (HHS) is characterized by severe hyperglycemia and hyperosmolality without significant ketosis and acidosis.

  • The discrimination between HHS of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in initial presentation is difficult.

  • Pediatrician should suspect T1DM in patients with HHS but not obesity.

  • Age, clinical history and body type are helpful for identifying T1DM and HHS.

  • Children with T1DM are very sensitive to insulin treatment, and even appropriate amount of insulin may result in dramatically decreasing blood sugar levels.

Open access

Saurabh Uppal, James Blackburn, Mohammed Didi, Rajeev Shukla, James Hayden and Senthil Senniappan

Summary

Beckwith–Wiedemann syndrome (BWS) can be associated with embryonal tumours and congenital hyperinsulinism (CHI). We present an infant with BWS who developed congenital hepatoblastoma and Wilms’ tumour during infancy. The infant presented with recurrent hypoglycaemia requiring high intravenous glucose infusion and was biochemically confirmed to have CHI. He was resistant to diazoxide but responded well to octreotide and was switched to Lanreotide at 1 year of age. Genetic analysis for mutations of ABCC8 and KCNJ11 were negative. He had clinical features suggestive of BWS. Methylation-sensitive multiplex ligation-dependent probe amplification revealed hypomethylation at KCNQ1OT1:TSS-DMR and hypermethylation at H19 /IGF2:IG-DMR consistent with mosaic UPD(11p15). Hepatoblastoma was detected on day 4 of life, which was resistant to chemotherapy, requiring surgical resection. He developed Wilms’ tumour at 3 months of age, which also showed poor response to induction chemotherapy with vincristine and actinomycin D. Surgical resection of Wilms’ tumour was followed by post-operative chemotherapy intensified with cycles containing cyclophosphamide, doxorubicin, carboplatin and etoposide, in addition to receiving flank radiotherapy. We report, for the first time, an uncommon association of hepatoblastoma and Wilms’ tumour in BWS in early infancy. Early onset tumours may show resistance to chemotherapy. UPD(11p15) is likely associated with persistent CHI in BWS.

Learning points:

  • Long-acting somatostatin analogues are effective in managing persistent CHI in BWS.

  • UPD(11)pat genotype may be a pointer to persistent and severe CHI.

  • Hepatoblastoma and Wilms’ tumour may have an onset within early infancy and early tumour surveillance is essential.

  • Tumours associated with earlier onset may be resistant to recognised first-line chemotherapy.

Open access

Sarah Kiff, Carolyn Babb, Maria Guemes, Antonia Dastamani, Clare Gilbert, Sarah E Flanagan, Sian Ellard, John Barton, M Dattani and Pratik Shah

Summary

We report a case of partial diazoxide responsiveness in a child with severe congenital hyperinsulinaemic hypoglycaemia (CHI) due to a homozygous ABCC8 mutation. A term baby, with birth weight 3.8 kg, born to consanguineous parents presented on day 1 of life with hypoglycaemia. Hypoglycaemia screen confirmed CHI. Diazoxide was commenced on day 7 due to ongoing elevated glucose requirements (15 mg/kg/min), but despite escalation to a maximum dose (15 mg/kg/day), intravenous (i.v.) glucose requirement remained high (13 mg/kg/min). Genetic testing demonstrated a homozygous ABCC8 splicing mutation (c.2041-1G>C), consistent with a diffuse form of CHI. Diazoxide treatment was therefore stopped and subcutaneous (s.c.) octreotide infusion commenced. Despite this, s.c. glucagon and i.v. glucose were required to prevent hypoglycaemia. A trial of sirolimus and near-total pancreatectomy were considered, however due to the significant morbidity potentially associated with these, a further trial of diazoxide was commenced at 1.5 months of age. At a dose of 10 mg/kg/day of diazoxide and 40 µg/kg/day of octreotide, both i.v. glucose and s.c. glucagon were stopped as normoglycaemia was achieved. CHI due to homozygous ABCC8 mutation poses management difficulties if the somatostatin analogue octreotide is insufficient to prevent hypoglycaemia. Diazoxide unresponsiveness is often thought to be a hallmark of recessively inherited ABCC8 mutations. This patient was initially thought to be non-responsive, but this case highlights that a further trial of diazoxide is warranted, where other available treatments are associated with significant risk of morbidity.

Learning points:

  • Homozygous ABCC8 mutations are commonly thought to cause diazoxide non-responsive hyperinsulinaemic hypoglycaemia.

  • This case highlights that partial diazoxide responsiveness in homozygous ABCC8 mutations may be present.

  • Trial of diazoxide treatment in combination with octreotide is warranted prior to considering alternative treatments, such as sirolimus or near-total pancreatectomy, which are associated with more significant side effects.

Open access

Miriam Hinaa Ahmad and Ismat Shafiq

Summary

We report a case of a 21-year-old African American female with history of pre-diabetes, and a diagnosis of a rare leukemia, blastic-plasmacytoid dendritic neoplasm (BPDCN), who developed diabetic ketoacidosis (DKA) after the third dose of PEG-asparaginase infusion. She was successfully treated with insulin. Asparaginase is a vital part of treatment protocols for acute lymphoblastic leukemia (ALL) in combination with other chemotherapeutic drugs. Asparaginase therapy has been reported to cause hyperglycemia especially when used in conjunction with glucocorticoids for the treatment of ALL in the pediatric population. Multiple mechanisms for hyperglycemia have been hypothesized which include decreased insulin secretion, impaired insulin receptor function and excess glucagon formation. Hyperglycemia is usually self-limiting but can deteriorate to diabetic ketoacidosis. DKA is a rare adverse effect with asparaginase therapy with an incidence rate of about 0.8%.

Learning points:

  • DKA is a rare finding following asparaginase therapy.

  • Hyperglycemia is most commonly seen with asparaginase treatment when used along with glucocorticoid.

  • Frequent blood glucose monitoring and prompt initiation of insulin treatment with hyperglycemia can prevent severe complications.

  • Patients and physician education on this complication can reduce morbidity due to DKA.

Open access

Ming Li Yee, Rosemary Wong, Mineesh Datta, Timothy Nicholas Fazio, Mina Mohammad Ebrahim, Elissa Claire Mcnamara, Gerard De Jong and Christopher Gilfillan

Summary

Mitochondrial diseases are rare, heterogeneous conditions affecting organs dependent on high aerobic metabolism. Presenting symptoms and signs vary depending on the mutation and mutant protein load. Diabetes mellitus is the most common endocrinopathy, and recognition of these patients is important due to its impact on management and screening of family members. In particular, glycemic management differs in these patients: the use of metformin is avoided because of the risk of lactic acidosis. We describe a patient who presented with gradual weight loss and an acute presentation of hyperglycemia complicated by the superior mesenteric artery syndrome. His maternal history of diabetes and deafness and a personal history of hearing impairment led to the diagnosis of a mitochondrial disorder.

Learning points:

  • The constellation of diabetes, multi-organ involvement and maternal inheritance should prompt consideration of a mitochondrial disorder.

  • Mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS) and maternally inherited diabetes and deafness (MIDD) are the most common mitochondrial diabetes disorders caused by a mutation in m.3243A>G in 80% of cases.

  • Metformin should be avoided due to the risk of lactic acidosis.

  • There is more rapid progression to insulin therapy and higher prevalence of diabetic complications compared to type 2 diabetes.

  • Diagnosis of a mitochondrial disorder leads to family screening, education and surveillance for future complications.

  • Superior mesenteric artery syndrome, an uncommon but important cause of intestinal pseudo-obstruction in cases of significant weight loss, has been reported in MELAS patients.

Open access

Sebastian Hörber, Sarah Hudak, Martin Kächele, Dietrich Overkamp, Andreas Fritsche, Hans-Ulrich Häring, Andreas Peter and Martin Heni

Summary

Diabetic ketoacidosis is a life-threatening complication of diabetes mellitus. It usually occurs in patients with type 1 diabetes where it is typically associated with only moderately increased blood glucose. Here, we report the case of a 52-year-old female patient who was admitted to the emergency unit with severely altered mental status but stable vital signs. Laboratory results on admission revealed very high blood glucose (1687 mg/dL/93.6 mmol/L) and severe acidosis (pH <7) with proof of ketone bodies in serum and urine. Past history revealed a paranoid schizophrenia diagnosed 10 years ago and for which the patient was treated with risperidone for many years. Acute treatment with intravenous fluids, intravenous insulin infusion and sodium bicarbonate improved the symptoms. Further laboratory investigations confirmed diagnosis of autoimmune type 1 diabetes. After normalization of blood glucose levels, the patient could soon be discharged with a subcutaneous insulin therapy.

Learning points:

  • Diabetic ketoacidosis as first manifestation of type 1 diabetes can occur with markedly elevated blood glucose concentrations in elder patients.

  • Atypical antipsychotics are associated with hyperglycemia and an increased risk of new-onset diabetes.

  • First report of risperidone-associated diabetic ketoacidosis in new-onset type 1 diabetes.

  • Patients treated with atypical antipsychotics require special care and regular laboratory examinations to detect hyperglycemia and diabetic ketoacidosis.

  • In cases when the diagnosis is in doubt, blood gas analysis as well as determination of C-peptide and islet autoantibodies can help to establish the definite diabetes type.

Open access

Gordon Sloan, Tania Kakoudaki and Nishant Ranjan

Summary

We report a case of a 63-year-old man who developed diabetic ketoacidosis (DKA) associated with canagliflozin, a sodium glucose co-transporter 2 (SGLT-2) inhibitor. He presented acutely unwell with a silent myocardial infarction, diverticulitis and DKA with a minimally raised blood glucose level. Standard therapy for DKA was initiated. Despite this, ketonaemia persisted for a total of 12 days after discontinuation of canagliflozin. Glucosuria lasting for several days despite discontinuation of the medications is a recognised phenomenon. However, this is the longest duration of ketonaemia to be reported. The cause of prolonged SGLT-2 inhibition remains uncertain. Deviation from the normal DKA treatment protocol and use of personalised regimens may be required in order to prevent relapse into ketoacidosis while avoiding hypoglycaemia in those that develop this condition.

Learning points:

  • Diabetic ketoacidosis (DKA) may develop in the presence of lower-than-expected blood glucose levels in patients treated with a sodium glucose co-transporter 2 (SGLT-2) inhibitor.

  • Certain individuals prescribed with SGLT-2 inhibitors may be more at risk of DKA, for example, those with a low beta cell function reserve, excessive alcohol consumption and a low carbohydrate diet.

  • In order to reduce the risk of SGLT-2 inhibitor-associated DKA, all patients must be carefully selected before prescription of the medication and appropriately educated.

  • Increased serum ketone levels and glucosuria have been reported to persist for several days despite discontinuation of their SGLT-2 inhibitor.

  • Physicians should consider individualised treatment regimens for subjects with prolonged DKA in the presence of SGLT-2 inhibition.

Open access

Clarissa Ern Hui Fang, Mohammed Faraz Rafey, Aine Cunningham, Sean F Dinneen and Francis M Finucane

Summary

A 28-year-old male presented with 2 days of vomiting and abdominal pain, preceded by 2 weeks of thirst, polyuria and polydipsia. He had recently started risperidone for obsessive-compulsive disorder. He reported a high dietary sugar intake and had a strong family history of type 2 diabetes mellitus (T2DM). On admission, he was tachycardic, tachypnoeic and drowsy with a Glasgow Coma Scale (GCS) of 10/15. We noted axillary acanthosis nigricans and obesity (BMI 33.2 kg/m2). Dipstick urinalysis showed ketonuria and glycosuria. Blood results were consistent with diabetic ketoacidosis (DKA), with hyperosmolar state. We initiated our DKA protocol, with intravenous insulin, fluids and potassium, and we discontinued risperidone. His obesity, family history of T2DM, acanthosis nigricans and hyperosmolar state prompted consideration of T2DM presenting with ‘ketosis-prone diabetes’ (KPD) rather than T1DM. Antibody markers of beta-cell autoimmunity were subsequently negative. Four weeks later, he had modified his diet and lost weight, and his metabolic parameters had normalised. We reduced his total daily insulin dose from 35 to 18 units and introduced metformin. We stopped insulin completely by week 7. At 6 months, his glucometer readings and glycated haemoglobin (HbA1c) level had normalised.

Learning points:

  • Risperidone-induced diabetic ketoacidosis (DKA) is not synonymous with type 1 diabetes, even in young white patients and may be a manifestation of ‘ketosis-prone’ type 2 diabetes (KPD).

  • KPD is often only confirmed after the initial presentation, when islet autoimmunity and cautious phasing out of insulin therapy have been assessed, and emergency DKA management remains the same.

  • As in other cases of KPD, a family history of T2DM and presence of cutaneous markers of insulin resistance were important clinical features suggestive of an alternative aetiology for DKA.

Open access

Gordon Sloan, Amjad Ali and Jonathan Webster

Summary

Ketoacidosis occurring during lactation has been described infrequently. The condition is incompletely understood, but it appears to be associated with a combination of increased metabolic demands during lactation, reduction in carbohydrate intake and acute illness. We present a case of a 27-year-old woman, 8 weeks post-partum, who was exclusively breastfeeding her child whilst following a low carbohydrate diet. She developed gastroenteritis and was unable to tolerate an oral diet for several days. She presented with severe metabolic acidosis on admission with a blood 3-hydroxybutyrate of 5.4 mmol/L. She was treated with intravenous dextrose and intravenous sodium bicarbonate, and given dietary advice to increase her carbohydrate intake. She made a rapid and full recovery. We provide a summary of the common causes of ketoacidosis and compare our case with other presentations of lactation ketoacidosis.

Learning points:

  • Ketoacidosis in the lactating woman is a rare cause of raised anion gap metabolic acidosis.

  • Low carbohydrate intake, starvation, intercurrent illness or a combination of these factors could put breastfeeding women at risk of ketoacidosis.

  • Ketoacidosis in the lactating woman has been shown to resolve rapidly with sufficient carbohydrate intake and intravenous dextrose.

  • Early diagnosis and prompt treatment are essential because the condition is reported to be reversible with a low chance of recurrence with appropriate dietary advice.

Open access

Dinesh Giri, Prashant Patil, Rachel Hart, Mohammed Didi and Senthil Senniappan

Summary

Poland syndrome (PS) is a rare congenital condition, affecting 1 in 30 000 live births worldwide, characterised by a unilateral absence of the sternal head of the pectoralis major and ipsilateral symbrachydactyly occasionally associated with abnormalities of musculoskeletal structures. A baby girl, born at 40 weeks’ gestation with birth weight of 3.33 kg (−0.55 SDS) had typical phenotypical features of PS. She had recurrent hypoglycaemic episodes early in life requiring high concentration of glucose and glucagon infusion. The diagnosis of congenital hyperinsulinism (CHI) was biochemically confirmed by inappropriately high plasma concentrations of insulin and C-peptide and low plasma free fatty acids and β-hydroxyl butyrate concentrations during hypoglycaemia. Sequencing of ABCC8, KCNJ11 and HNF4A did not show any pathogenic mutation. Microarray analysis revealed a novel duplication in the short arm of chromosome 10 at 10p13–14 region. This is the first reported case of CHI in association with PS and 10p duplication. We hypothesise that the HK1 located on the chromosome 10 encoding hexokinase-1 is possibly linked to the pathophysiology of CHI.

Learning points:

  • Congenital hyperinsulinism (CHI) is known to be associated with various syndromes.

  • This is the first reported association of CHI and Poland syndrome (PS) with duplication in 10p13–14.

  • A potential underlying genetic link between 10p13–14 duplication, PS and CHI is a possibility.