One hundred years ago: the dawning of the insulin era.

The dawn of the insulin era can be placed in 1921, when Banting and Best started their experiments which led, a year later, to the successful treatment of diabetes. They were preceded by the discoveries of the pancreatic cause of diabetes by Minkowski and von Mering in 1889 and of the islets by Paul Langerhans in 1869. The achievement of the first targeted treatment in medical history was a landmark of medical progress. However, it was accompanied by a mixture of human greatness and misery. Genius and recklessness, ambition and deception, camaraderie and rivalry, selflessness and pursuit of glory went along with superficial search of the existing literature, poor planning, faulty interpretation of results, failure to reproduce them, and misquoting of reports from other laboratories. Then as now, such faults surface whenever human nature aims to push forward the boundaries of knowledge and pose a real challenge in today's world, as the scientific method strives to keep healthy in the face of growing anti-scientific feelings.

[Insulin: initiation of pool of insulin-dependent cells, targeted transfer of triglycerides and increase of kinetic parameters of oxidation of fatty acids].

The insulin, to provide with energy the biological function of locomotion, formed: a) pool of phylogenetically late insulin-dependent cells; b) highly productive vector variant of transfer of saturated and mono unsaturated fatty acids only to insulin-dependent cells; c) new variant of active absorption of substrates for acquiring energy by cells--apoE/B-100-receptor endocytosis; d) transformation of all endogenically synthesized palmitic saturated fatty acid in oleic mono saturated fatty acid and e) replacement of potentially ineffective palmitic variant of formation of energy in vivo with potentially high-performance oleic variant of metabolism of substrates for turning out of ATP. The insulin expressed synthesis of apoE glucose carrier 4 and stearyl-KoA-desaturase. These occurrences confirm that syndrome of insulin resistance primarily is the pathology of metabolism of fatty acids and only secondary the pathology metabolism of glucose. The multi-functional fatty cells of visceral areolar tissue and specialized adipocytes of subcutaneous fat depots are phylogenetically, regulatory and functionally different cells. They are formed under development of different biological functions: the first ones under realization of biological function of trophology and second ones under realization of biological function of locomotion. At the level of organism, the mechanisms of hypothalamus-fatty cells feedback are realized by peptide leptin and in case of hypothalamus-adipocytes feedback--peptide adiponectin. The potential possibilities of mitochondria in synthesis of ATP are high and are conditioned only by amount of substrate of mitochondria acetyl-KoA. This shortage can be chronic as in cases of disorder of insulin function and palmitic variant of metabolism of substrates for acquiring energy by cells. The deficiency of acetyl-KoA can be acute as is the case of diabetic coma when surplus amount of ketonic bodies follows the expressed deficiency of acetyl-KoA formed from glucose and fatty acids. Can the intravenous injection of acetyl-KoA be effective under diabetic ketoacidosic coma?

Catecholamine-resistant shock and hypoglycemic coma after cardiotomy in a patient with unexpected isolated ACTH deficiency.

Isolated adrenocorticotropic hormone (ACTH) deficiency is an extremely rare disease in which ACTH-producing cells of the pituitary gland are selectively damaged. The resulting decline in ACTH production and secretion results in chronic secondary adrenocortical insufficiency. The patient in this case did not present with adrenal insufficiency symptoms prior to surgery. However, after cardiotomy under extracorporeal circulation, the patient lapsed into a catecholamine-resistant shock and hypoglycemic coma. Acute adrenal insufficiency was strongly suspected, and the patient was diagnosed with isolated ACTH deficiency after careful examination. Because the demand for cortisol increases after highly invasive surgeries, cortisol supplementation therapy is essential for patients with complications from isolated ACTH deficiency. There is a high risk of a lethal outcome when surgery is carried out without a diagnosis, as in this case. Therefore, cortisol must be supplemented without delay when acute adrenal insufficiency is suspected during the perioperative period.

[Hypoglycaemic coma due to falsely elevated glucose values in a patient with diabetes mellitus and peritoneal dialysis]. / Hypoglykemisch coma als gevolg van foutiefverhoogde glucosewaarden bij een patiënte met diabetes mellitus en peritoneale dialyse.

A 45-year-old female diabetes-mellitus patient on peritoneal dialysis was admitted because of vertigo. During her stay in hospital she developed a comatose condition with abnormal head posture and deviation ofthe eyes to the left. Capillary blood from the fingertip showed a glucose value of 15.4 mmol/l. However, the automatically obtained glucose value delivered with a blood-gas analysis was found to be 1.2 mmol/l. The neurological state of the patient normalised fully after intravenous glucose administration. The glucose values were falsely elevated because the patient used a peritoneal dialysis fluid at night which contained icodextrin as an osmotic agent. Metabolites of icodextrin can influence blood-glucose measurements taken using analyzers that depend on the enzyme glucose dehydrogenase. To prevent potentially life-threatening situations, the use of an adequate glucose meter is of paramount importance.

Profound hypokalemia in diabetic ketoacidosis: a therapeutic challenge.

OBJECTIVE: To describe profound hypokalemia in a comatose patient with diabetic ketoacidosis. METHODS: We present a case report, review the mechanisms for the occurrence of hypokalemia in diabetic ketoacidosis, and discuss its management in the setting of hyperglycemia and hyperosmolality. RESULTS: A 22-year-old woman with a history of type 1 diabetes mellitus was admitted in a comatose state. Laboratory tests revealed a blood glucose level of 747 mg/dL, serum potassium of 1.9 mEq/L, pH of 6.8, and calculated effective serum osmolality of 320 mOsm/kg. She was intubated and resuscitated with intravenously administered fluids. Intravenous administration of vasopressors was necessary for stabilization of the blood pressure. Intravenous infusion of insulin was initiated to control the hyperglycemia, and repletion of total body potassium stores was undertaken. A total of 660 mEq of potassium was administered intravenously during the first 12.5 hours. Despite such aggressive initial repletion of potassium, the patient required 40 to 80 mEq of potassium daily for the next 8 days to increase the serum potassium concentration to normal. CONCLUSION: Profound hypokalemia, an uncommon initial manifestation in patients with diabetic ketoacidosis, is indicative of severe total body potassium deficiency. Under such circumstances, aggressive potassium repletion in a comatose patient must be undertaken during correction of other metabolic abnormalities, including hyperglycemia and hyperosmolality. Intravenously administered insulin should be withheld until the serum potassium concentration is (3)3.3 mEq/L.

[Diabetic coma and hypoglycemia in children. What to do when in an emergency]. / Diabetes-komplikationen bei Kindern. Nach dem Fussballspiel: Insulinbedarf falsch eingeschätzt.

With a few very rare exceptions, hypoglycemia and diabetic coma almost always occur in patients with diabetes mellitus, and are among the most common emergencies in children. For the emergency physician, it is important, on the basis of a specific history-taking and information from, for example, family members, supplemented by a clinical examination done in the light of knowledge of the typical symptoms of each of the entities, to determine whether hypoglycemia or diabetic coma is presenting. The most important technical examination is the measurement of blood glucose. In the event of hypoglycemia, the first therapeutic measure is the administration of sugar--in the case of a comatose patient via a venous line. The s.c. or i.m. administration of glucagon to achieve short-term improvement might be considered. In the event of a diabetic coma, abundant electrolyte solution is initially needed, followed by i.v. insulin. Referral to hospital is mandatory.

Diabetic keto-acidotic (DKA) coma following olanzapine initiation in a previously euglycaemic woman and successful continued therapy with olanzapine.

We report the case of a euglycaemic woman whose glucose control rapidly decompensated following olanzapine initiation leading to diabetic coma. Hyperglycaemia has been associated with chronic psychotic disorders and antipsychotics for many years. However, it is unusual to see such rapid and life-threatening changes associated with treatment. The case highlights that changes in antipsychotic treatment may be associated with large changes in glucose tolerance, and that it is possible to continue antipsychotic treatment with appropriate diabetic care.

Reversal of foetal hydrops and foetal tachyarrhythmia associated with maternal diabetic coma.

Foetal hydrops is always a challenge for the clinician. We report a case of tachycardia associated with hydrops and hydramnios in a pregnancy complicated with diabetic coma at 28 weeks gestation. Normal foetal heart rate was recorded immediately after correction of maternal acidotic status and hydrops eventually disappeared. The woman was delivered at 32 weeks and the baby had an uncomplicated postnatal course. We hypothesise that maternal ketoacidosis has been the precipitating factor of tachycardia and congestive heart failure and that this case is conceptually similar to the "late death" phenomenon, reported in cases of poorly controlled maternal diabetes.

Acute renal failure due to rhabdomyolysis in diabetic patients.

We report a 32-year-old Black man, admitted to the ICU with coma and severe metabolic disturbances due to diabetic ketoacidosis. During the admission, rhabdomyolysis and acute renal failure (ARF) were diagnosed. After metabolic control and gradual decrease of creatine kinase levels, he presented a progressive improvement of renal function. We emphasize nontraumatic rhabdomyolysis as a poorly recognized pathogenetic factor for ARF in diabetic ketoacidosis and suggest that a better understanding of its mechanisms and an early application of protective measures is necessary.

Motor aphasia due to prolonged hypoglycaemic coma in a patient with insulin-dependent diabetes mellitus.

A 45-year-old insulin-dependent diabetic man was in a hypoglycaemic coma for one month but recovered after continuous infusion of glucose and insulin. An isolated neurological deficit, motor aphasia, persisted after recovery from the coma. Repeated computerized tomography did not demonstrate any abnormal findings attributable to coma or aphasia. Precise follow-up examinations of aphasia showed improvement of Broca type motor aphasia to transcortical motor aphasia. Hypoglycaemic aphasia in a patient after recovery from prolonged coma is rare and its clinical course and pathogenesis are discussed with reference to the available literature.

[Intracranial hypertension in severe diabetic ketoacidosis with coma. Two cases]. / Hypertension intracrânienne au cours de l'acidocétose diabétique grave avec coma. Deux observations.

We observed two cases of severe diabetic ketoacidosis with coma and shock. In one case, coma was present at admission and in the second occurred within 15 hours. In both cases, intracranial hypertension was confirmed with an extradural captor. These findings are in agreement with observations of brain oedema in diabetic ketoacidosis with coma. Clinical data suggest that brain oedema may occur after a latency period but that clinical expression is much more rare, perhaps favoured by treatment (excessive rehydratation, alkalinization, too sharp drop in blood glucose level). In our cases, despite major fluid infusion, shock persisted requiring norepinephrine. This shock could have been the expression of the severe ketoacidosis or have resulted from an underlying infection. In case of sudden onset coma, a regularly encountered manifestation of brain oedema, respiratory assistance and mannitol infusion must be instituted rapidly. With this type of management, it should be possible to improve the severe prognosis of brain oedema in diabetic ketoacidosis.

[Diabetic coma and bases of proper treatment]. / A diabeteses coma és kezelésének alapjai.

Hyperglycaemic, hyperosmolar coma developing in diabetes mellitus-with or without ketoacidosis-is a perilous metabolic catastrophe, preserving its clinical importance even nowadays. The features of the two basic forms of diabetic coma, the development and characteristics of clinical symptoms and laboratory alterations caused by absolute or relative lack of insulin are reported by the author. The importance of early diagnosis and up-to-date intensive treatment is emphasized, regarding the need of decreasing of the still now considerable mortality rate. Fundamental principles of the therapeutic interventions are the following: improvement of the microcirculation through appropriate compensation of fluid and elektrolytes, intravenous or intramuscular administration of low-dose insulin, prevention of hypokalemic condition, and correction of acidosis under pH 7,1 value. Moreover, the well-planned supportive treatment is also essential: prevention of thromboembolism, averting the occasional development of shock caused usually by infections, and prophylaxis of the often fatal cerebral oedema. The estimation and follow-up of osmolality and the prevention of rapid changes in serum glucose and electrolyte levels are of particular importance in every cases. Careful observation of the patients regarding the cardiorespiratory and renal functions is of great significance in both (first and second) phases of the treatment. Improvement of patients' education, controlled care of diabetic patients, reduction of the number of recidive cases and increasing knowledge regarding diabetes among the general practitioners are determined by the author as the future possibilities for the prevention of this severe metabolic disorder.