Diabetic ketoacidosis: an overlooked child killer in sub-Saharan Africa?

The true incidence of diabetic ketoacidosis (DKA) in sub-Saharan Africa is unknown but unlike in the Western countries, DKA is also uniquely frequent among type 2 diabetes patients of African origin. Increased hyperglycaemia and hepatic ketogenesis lead to osmotic diuresis, dehydration and tissue hypoxia. Acute complications of DKA include cerebral oedema, which may be compounded by malnutrition, parasitic and microbial infections with rampant tuberculosis and HIV. Overlapping symptoms of these conditions and misdiagnosis of DKA contribute to increased morbidity and mortality. Inability of the patients to afford insulin treatment leads to poor glycemic control as some patients seek alternative treatment from traditional healers or use herbal remedies further complicating the disease process. Standard treatment guidelines for DKA currently used may not be ideal as they are adapted from those of the developed world. Children presenting with suspected DKA should be screened for comorbidities which may complicate fluid and electrolyte replacement therapy protocol. Patient rehabilitation should take into account concurrent treatment for infectious conditions to avoid possible life-threatening drug interactions. We recommend that health systems in sub-Saharan Africa leverage the Expanded Immunization Programme or TB/HIV/AIDS programmes, which are fairly well entrenched to support diabetes services.

Grapefruit juice improves glycemic control but exacerbates metformin-induced lactic acidosis in non-diabetic rats.

Recent clinical studies have indicated that grapefruit juice (GFJ) improves insulin resistance and reduces weight gain in humans. The effect of GFJ on glucose tolerance and metformin-induced lactic acidosis in normal, non-diabetic in rats is hereby investigated. Three groups (A, B, C) of 20 male Wistar rats each, were treated with stepwise, escalated oral doses of 0, 1.0, 2.0, 3.0 (group A), and 3.0 ml/kg body weight (groups B and C) of GFJ. Group C rats additionally received 250 mg/kg body weight of metformin. All the animals were sacrificed after 14 days of treatment. Fasting blood glucose levels were significantly (P < 0.0001) lower in GFJ-treated test (2.9 +/- 0.4 mmol/L) compared with control (3.7 +/- 0.39 mmol/L) rats, but 1.5-hr plasma insulin levels were similar. GFJ alone or in combination with metformin, significantly (P < 0.05) lowered blood glucose levels compared with control animals. Blood lactic acid levels were similar in GFJ-treated test (2.81 +/- 1.4 mmol/L) and control (2.54 +/- 0.7 mmol/L) rats, respectively, but were significantly increased (P = 0.0079) in rats that were treated with either metformin alone (5.38 +/- 2.53 mmol/L) or in combination with GFJ (8.31 +/- 3.48 mmol/L). Metformin concentration in liver tissue was significantly higher (P < 0.05) in GFJ-treated (397 +/- 19 microg/g) than in control (280 +/- 15 microg/g) rats, respectively. Plasma metformin levels were comparable between the control (95 +/- 8.1 microg/ml) and GFJ-treated test (108 +/- 20 microg/ml) rats, respectively. Liver tissue metformin concentrations and plasma lactic acid levels showed significant correlation in both control (P = 0.0122; r(2) = 0.9080) and GFJ-treated test rats (P = 0.0005; r(2) = 0.9893). Although GFJ may be beneficial to diabetic patients, it may exacerbate lactic acidosis in diabetic patients taking metformin concurrently.

Colonic energy salvage in chronic pancreatic exocrine insufficiency.

BACKGROUND: Chronic pancreatic exocrine insufficiency results in maldigestion. As a result, increased amounts of undigested nutrients reach the colon, providing more substrate for bacterial fermentation to produce short-chain fatty acids, which could therefore provide additional energy supplement. METHODS: This study aimed to assess carbohydrate malabsorption in patients with chronic pancreatic exocrine insufficiency after ingestion of a standard diet and to calculate energy salvaged by colonic bacterial metabolism. A 72-hour stool collection was done on 10 adult patients receiving a 3-day standard diet containing 100 g fat, 329 g carbohydrate, and 154 g protein, and short-chain fatty acids, fat, carbohydrate, and nitrogen excretion were assessed. A breath hydrogen test after ingestion of 200 g (dry weight) cooked maize meal (test meal) and 10 g oral inulin (standard), respectively, was subsequently done on the patients and 15 healthy adult controls. RESULTS: Breath hydrogen production after ingestion of maize meal and inulin, respectively, and calculated carbohydrate malabsorption were significantly greater in patients (21.4% +/- 17%) than in controls (10.2 +/- 1.4%; p < .05). Patients malabsorbed 70.4 g/d (281.6 kcal) carbohydrate in the standard diet. Total carbohydrate loss in stool amounted to 8.1 g/d (2.4%), and 62.3 g/d (19%) was hence salvaged as short-chain fatty acids for energy provision. Colonic bacterial fermentation therefore converted 88.5% of malabsorbed carbohydrate to short-chain fatty acids, 92.8% of which was absorbed and 7.2% excreted. This suggests that 10.2% of energy expenditure/requirement in these patients is derived from salvage of malabsorbed carbohydrate. CONCLUSIONS: Colonic bacterial metabolism is a significant source of energy salvage in patients with pancreatic enzyme deficiency.

Comparison of inulin and lactulose as reference standards in the breath hydrogen test assessment of carbohydrate malabsorption in patients with chronic pancreatic exocrine insufficiency.

Although often used as a reference standard in the breath hydrogen test (BHT), lactulose fermentation produces more hydrogen, compared to starch, and may therefore not be ideal. This study compares inulin with lactulose as reference standard in the study of carbohydrate malabsorption. Seventeen patients with malabsorption due to chronic pancreatitis and 15 normal controls were studied. Following overnight fasts, BHTs were performed after ingesting 10 g lactulose, 10 g inulin, and 200 g (16 g highly resistant starch) maize meal. Lactulose fermentation produced significantly more hydrogen than inulin in patients with malabsorption (97 +/- 20 vs 45 +/- 22 ppm x hr; P < 0.05) and controls (43 +/- 18 vs 21 +/- 10 ppm x hr; P < 0.05). Patients produced more hydrogen than controls with both standards (lactulose, 97 +/- 20 vs 43 +/- 18 ppm x hr, P < 0.05; inulin 45 +/- 22 vs 21 +/- 10 ppm x hrs; P < 0.05), suggesting adaptation of the colonic flora. Calculated CHO malabsorption was 2.5 +/- 0.8 vs 5.2 +/- 3.8 g with lactulose and 5.2 +/- 3.1 vs 11.2 +/- 9.6 g with inulin as standards in controls and patients, respectively (P < 0.05). Lactulose produces more breath hydrogen than inulin. Calculation of CHO malabsorption using these standards is therefore not comparable.