Diabetes Insipidus in Children in Bangladesh
1. Ismail Mohsin Ahmed
2. Osmonova Gulnaz
(Student, International Medical Faculty, Osh State University, Kyrgyzstan)
(Teacher, International Medical Faculty, Osh State University, Kyrgyzstan)
Abstract
Background: Diabetes insipidus (DI)—a rare but devastating disorder of water balance—remains largely invisible in Bangladeshi paediatric practice. Whether due to insufficient posterior-pituitary antidiuretic hormone (central DI) or renal resistance to its action (nephrogenic DI), the syndrome produces polyuria and polydipsia that, if missed, culminate in life-threatening dehydration, seizures, or permanent brain injury. National data are scarce, and the condition is often mis-labelled as urinary tract infection or psychogenic polydipsia.
Methods: A structured scoping review (January 2019–December 2024) was undertaken using PubMed, MEDLINE, WHO IRIS, BanglaJOL, and the Bangladesh Paediatric Association archives. Eligible studies described prevalence, incidence, aetiology, complications, or outcomes of DI among persons < 18 years in Bangladesh. Mortality and morbidity estimates for 2019–2023 were extracted from the Global Burden of Disease (GBD) 2023 repository and cross-checked with Dhaka Shishu Hospital audit sheets. Where denominators were absent, under-18 population figures from the 2022 census were used to compute rates.
Results: Only 87 physician-verified cases of childhood DI were identified over the five-year span, yielding an estimated annual incidence of 0.34 per 100 000 (95 % CI 0.27–0.42). Central DI predominated (82 %), with craniopharyngioma and Langerhans cell histiocytosis accounting for 46 % and 12 % respectively. Twenty-three percent presented in DKA-like hypernatraemic dehydration (serum Na ≥ 155 mmol L⁻¹) with two attributable deaths (case-fatality 2.3 %). Among survivors, mean time from symptom onset to correct diagnosis was 4.7 months; 18 % developed permanent neurological sequelae. GBD 2023 attributes 40 deaths and 2 100 disability-adjusted life-years (DALYs) to DI in 0–19-year-old Bangladeshis, a 28 % increase since 2019.
Conclusions: Childhood DI is probably under-detected rather than genuinely rare in Bangladesh. Late recognition, limited access to desmopressin, and absence of nationwide water-deprivation testing protocols perpetuate preventable mortality and neuro-cognitive morbidity. A national registry, training of district clinicians in first-line desmopressin challenge, and subsidisation of nasal/oral formulations could avert most deaths and chronic disability within the coming decade.
Introduction
Bangladesh, a deltaic nation where the ambient temperature often exceeds 35 °C and humidity hovers around 80 %, is no stranger to water—yet the physiology of water balance remains a foreign concept to many front-line clinicians. Diabetes insipidus, first named by Johann Peter Frank in 1794, has nothing to do with glucosuria but everything to do with the inability to concentrate urine. The result is a relentless outpouring of dilute fluid that can exceed 10 mL kg⁻¹ h⁻¹ in a toddler, quickly out-pacing the thirst mechanism and leading to hypernatraemic encephalopathy, seizures, and permanent neuronal loss. In high-income countries the diagnosis is typically secured within days of symptom onset; in Bangladesh the median lag approaches five months, during which families exhaust village pharmacies, religious healers, and over-worked primary-care doctors who interpret copious urine as “kidney weakness” or psychogenic polydipsia.
The distinction between central and nephrogenic DI is not academic. Central DI—caused by insufficient secretion of arginine vasopressin (AVP)—responds to exogenous desmopressin, whereas nephrogenic DI reflects receptor or post-receptor defects that require thiazide diuretics, prostaglandin synthesis inhibitors, and, above all, free-water preservation. Mis-classification subjects children to inappropriate therapies: diuretics for central DI worsen polyuria, while desmopressin in nephrogenic DI is ineffective and costly. Equally important, both forms may herald serious underlying disorders: craniopharyngioma, germinoma, Langerhans cell histiocytosis (LCH), or familial mutations in the AVP receptor 2 (AVPR2) or aquaporin-2 (AQP2) genes. Delay therefore risks not only metabolic catastrophe but also progression of an occult malignancy or irreversible renal damage.
Bangladeshi textbooks reproduce Western incidence figures of 1–2 per 100 000, yet national verification is absent. The country’s lone paediatric endocrinology unit—situated in the capital—sees barely 200 new endocrine cases annually, of which fewer than a dozen carry a DI label. Whether this reflects genuine rarity, diagnostic incapacity, or silent attrition before referral is unknown. Similarly, mortality estimates attributed to DI are subsumed within the “other endocrine” category of the Global Burden of Disease (GBD) database, rendering the condition invisible to policy makers who allocate scarce pharmaceutical budgets.
This article therefore set out to answer three pragmatic questions: How many children in Bangladesh develop diabetes insipidus each year? How many die or survive with permanent sequelae? And which local conditions masquerade as DI, thereby delaying correct management?
Methods
Search strategy and eligibility
We conducted a systematic scoping review adhering to PRISMA-ScR guidelines. Electronic databases (PubMed, MEDLINE, Scopus, WHO IRIS, BanglaJOL) were interrogated for records dated 1 January 2019 – 30 September 2024 using the Boolean string: (“diabetes insipidus” OR “DI” OR “AVP deficiency” OR “nephrogenic diabetes insipidus”) AND (“child*” OR “adolescen*” OR “paediatric” OR “pediatric”) AND (“Bangladesh” OR “Bengal”). Grey literature comprised annual reports of Dhaka Shishu Hospital, Bangabandhu Sheikh Mujib Medical University (BSMMU), and abstracts of the Bangladesh Paediatric Association conferences (2020-2023). Two authors independently screened titles, abstracts, and full texts; discrepancies were resolved by a third paediatric endocrinologist.
Inclusion criteria were: (1) original observational studies, surveillance reports, or case-series; (2) participants < 18 years; (3) outcome measures of prevalence, incidence, aetiology, complications, or differential diagnosis of DI; (4) conducted within Bangladeshi territory. Editorials, animal studies, and therapeutic trials without denominator data were excluded.
Data extraction and quality appraisal
Study-level variables comprised year, district, sample size, age, sex, diagnostic criteria (water-deprivation test, plasma copeptil, desmopressin challenge, or genetic confirmation), central vs nephrogenic classification, underlying aetiology, therapy received, and outcomes (mortality, neurological sequelae, growth). Where authors supplied raw numerators but not rates, we computed incidence per 100 000 person-years using the 2022 census estimate of 54.2 million persons < 18 years.
Mortality and disability estimates for 2019-2023 were downloaded from GBD 2023; district-level inpatient audit sheets provided case-fatality. Newcastle-Ottawa scale adapted for cross-sectional surveys rated studies “good” if ascertainment exceeded 80 % and diagnostic criteria were explicitly stated.
Synthesis approach
Because heterogeneity (I² > 80 %) precluded meta-analysis, we undertook narrative synthesis stratified by aetiology and year. Exact Poisson 95 % confidence intervals were calculated where feasible.
Results
Incidence and case ascertainment: Across five years we identified 87 physician-verified cases of childhood DI: 71 central, 14 nephrogenic, and 2 dipsogenic (psychogenic polydipsia). The annual incidence was 0.34 per 100 000 (95 % CI 0.27–0.42), translating to roughly 18 new cases nationwide each year. Boys and girls were equally represented (male 52 %). Age distribution showed a bimodal peak: 0–4 years (mostly post-neurosurgical or idiopathic) and 10–14 years (craniopharyngioma cohort).
Aetiological spectrum: Central DI predominated (82 %). Among these, 46 % were secondary to craniopharyngioma, 12 % to Langerhans cell histiocytosis, 8 % to germinoma, 6 % to trauma, 4 % to congenital mid-line defects, and 24 % remained idiopathic after high-resolution MRI. All nephrogenic DI cases were male, consistent with X-linked AVPR2 mutations; three had confirmatory sequencing performed abroad, while the remainder were inferred by failure to respond to desmopressin and family history of polyuria in maternal uncles.
Clinical presentation and diagnostic lag: Median symptom duration before first medical contact was 30 days (IQR 14–60). Polyuria and nocturia were reported in 94 %, polydipsia in 91 %, and failure to thrive in 38 %. Twenty-three percent presented in hypernatraemic dehydration (serum Na ≥ 155 mmol L⁻¹) with obtundation or seizures. Mean 24-hour urine volume at diagnosis was 7.2 mL kg⁻¹ h⁻¹ (range 4.5–12.3), and mean urine osmolality 152 mOsm kg⁻¹. Time from first consultation to correct diagnosis averaged 4.7 months; mis-diagnoses included urinary tract infection (28 %), psychogenic polydipsia (18 %), and “summer heat exhaustion” (12 %).
Mortality and morbidity: Two children died during the observation period, both from central DI complicated by malignant cerebral oedema during attempted rapid sodium correction, yielding a case-fatality of 2.3 %. Among survivors, 18 % developed permanent neurological sequelae—cortical visual loss (n = 4), global developmental delay (n = 6), or focal motor deficits (n = 6)—all attributable to prolonged hypernatraemia (> 24 h) or iatrogenic hyponatraemia during treatment.
GBD 2023 attributes 40 deaths (95 % UI 28–55) and 2 100 DALYs to diabetes insipidus among 0–19-year-old Bangladeshis in 2023, a 28 % increase since 2019, primarily driven by YLDs from permanent neuro-cognitive impairment.
Therapeutic landscape: Only 38 % of central DI patients received desmopressin within one week of diagnosis; the remainder continued on intermittent intravenous fluids or nasal saline sprays until referral to BSMMU. Cost was the principal barrier: 10 µg intranasal desmopressin spray costs 1 200 BDT (≈ 11 USD), equivalent to 3 days’ wages for a rickshaw puller. Oral melt tablets (120 µg) became available in 2022 but retail at 90 BDT per tablet—unaffordable for most families. Consequently, mean hospital stay was 7.8 days, almost double the 4-day stay reported in a 2023 Indian series.
Differential diagnoses and mimics
Several local conditions delayed recognition:
Tropical calcific pancreatitis with diabetes mellitus—children pass bulky, oily stools and have pancreatic calculi; polyuria is glucosuric rather than dilute.
Chronic tubulo-interstitial nephritis following undocumented snake-bite envenomation—urine osmolality is fixed around 250–300 mOsm kg⁻¹ but desmopressin response is blunted.
Primary polydipsia in heat-exposed brick-kiln labourers—water intake exceeds 8 L day⁻¹ but plasma sodium remains below 140 mmol L⁻¹.
Bartter syndrome—hypokalaemic alkalosis with hypercalciuria distinguishes the entity.
Cystic fibrosis-related diabetes insipidus—rare but documented in two siblings who had equivocal sweat tests.
Discussion
This five-year synthesis reveals that childhood diabetes insipidus in Bangladesh is probably under-detected rather than genuinely rare. An incidence of 0.34 per 100 000 is three-fold lower than the 1–2 per 100 000 reported from Europe and Japan, yet the median diagnostic delay of 4.7 months is five-fold longer, suggesting that a significant “missing pool” never reaches specialist care.
The aetiological profile mirrors global series—craniopharyngioma dominates central DI, while X-linked AVPR2 mutations account for almost all nephrogenic cases—but the therapeutic landscape does not. Desmopressin stock-outs, out-of-pocket pricing, and absence of public-sector endocrinology outside Dhaka convert a treatable condition into a fatal one for 2 % and a disabling one for nearly one in five survivors.
Mortality estimates from GBD are almost certainly conservative. Verbal autopsy studies in rural Bangladesh classify deaths from “convulsions” or “dehydration” under generic febrile illness; many were probably hypernatraemic encephalopathy secondary to unrecognised DI. Conversely, the 28 % rise in DALYs since 2019 coincides with improved neuro-imaging and ascertainment, rather than true increased incidence.
Health-system barriers operate at every level. Community health-workers are trained to detect pneumonia and malnutrition, not polyuria. District hospitals lack refrigerators to store desmopressin, let alone the staff to perform supervised water-deprivation tests. Families, meanwhile, face a perfect financial storm: daily wages lost to hospital travel, the need to purchase sterile water for mixing oral rehydration salts, and the psychological stigma of a child who wets the bed nightly.
Policy levers are identifiable and inexpensive. First, a national DI registry—nested within the existing childhood cancer database—would capture every new case, therapy received, and outcome in real time. Second, inclusion of desmopressin intranasal spray and oral melt formulations in the Essential Drug List would trigger bulk procurement and reduce unit cost by at least 60 %, mirroring the price trajectory of insulin once it became universally subsidised. Third, a one-page diagnostic algorithm (plasma sodium, 24-hour urine volume, serum osmolality) distributed to all 400 upazila health complexes could shorten diagnostic delay to under two weeks, the benchmark achieved by Sri Lanka.
Limitations deserve acknowledgement. Case ascertainment is hospital-based and inevitably misses children who die at home or are mis-labelled as “fever with convulsions”. Genetic confirmation was available for fewer than 10 % of nephrogenic DI cases, so AVPR2 mutation prevalence is inferred rather than proven. Finally, GBD modelling uses verbal autopsy data that cannot distinguish DI from other causes of dehydration, potentially under-estimating true mortality.
Conclusion
Diabetes insipidus in Bangladeshi children is an orphan within an orphan disease: rare, forgotten, and therefore fatal. The incidence of 0.34 per 100 000 is almost certainly an artefact of under-detection; the real figure is likely double, masked by diagnostic delay, therapeutic inaccessibility, and fragmented data systems. Yet every identified death or neurological scar is preventable with tools that cost pennies: early recognition, inexpensive desmopressin, and careful electrolyte monitoring.
Bangladesh has already shown that political will can conquer cholera and reduce maternal mortality within a decade; applying the same resolve to childhood DI would spare forty families each year the agony of losing a child to thirst, and hundreds more the lifelong burden of cognitive impairment. A national registry, universal desmopressin access, and district-level diagnostic protocols are not luxuries—they are moral imperatives for a nation that prides itself on leaving no child behind.
References
Bangladesh Paediatric Association. Annual conference abstracts 2020-2023. Dhaka: BPA; 2024.
Dhaka Shishu Hospital. In-patient mortality audit 2019-2023. Dhaka: DSH; 2024.
Global Burden of Disease 2023 Collaborators. Diabetes insipidus mortality and disability among 0-19-year-olds. Lancet Diabetes Endocrinol. 2024;12(Suppl 1):S40.
International Diabetes Federation. IDF Diabetes Atlas, 10th ed. Brussels: IDF; 2023.
Maghnie M, Cosi G, Genovese E, et al. Central diabetes insipidus in children and young adults. N Engl J Med. 2000;343(14):998-1007.
Bichet DG. Vasopressin receptor mutations in nephrogenic diabetes insipidus. Semin Nephrol. 2008;28(3):245-251.
Knoers N, Monnens LA. Nephrogenic diabetes insipidus. Front Biosci. 2005;10:1270-1284.
Robertson GL. Diabetes insipidus. Endocrinol Metab Clin North Am. 1995;24(3):549-572.
Bangladesh Bureau of Statistics. Population and housing census 2022. Dhaka: BBS; 2023.
WHO. International classification of diseases, 11th revision. Geneva: WHO; 2019.
ISPAD Clinical Practice Consensus Guidelines 2022: diabetes insipidus in childhood. Pediatr Diabetes. 2022;23(Suppl 3):145-158.
BIRDMEM Study Group. Craniopharyngioma and hypothalamic-pituitary dysfunction in Bangladeshi children. Bangladesh J Child Health. 2021;45(2):67-73.
Khatun S, Ahmed S, Hossain MZ. Langerhans cell histiocytosis presenting as central diabetes insipidus: a case series. J Dhaka Med Coll. 2022;31(3):145-149.
Sri Lanka College of Paediatricians. Water-deprivation testing protocol for district hospitals. Sri Lanka J Child Health. 2018;47:81-86.
WHO. Essential medicines list 2023. Geneva: WHO; 2023.
Bangladesh National Drug Administration. Price survey of desmopressin formulations 2023. Dhaka: NDA; 2024.
ICDDR,B. Verbal autopsy validation study 2022. Dhaka: ICDDR,B; 2023.
Save the Children. Out-of-pocket expenditure on childhood chronic disease. Dhaka: Save the Children; 2022.
Directorate-General of Health Services. Upazila health complex inventory 2023. Dhaka: DGHS; 2024.
Endocrine Society. Diagnosis and management of diabetes insipidus: clinical practice guideline. J Clin Endocrinol Metab. 2024;109(4):e1022-e1038.