[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.

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.

[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.

Experience with low-dose insulin infusion in diabetic ketoacidosis and diabetic hyperosmolarity.

Forty patients with diabetic ketoacidosis and eight patients with the diabetic hyperosmolar state were treated with low-dose insulin infusion in four teaching hospitals in the Cleveland area. The clinical and biochemical responses observed support previous favorable reports on this treatment modality. Two elderly patients with the hyperosmolar syndrome died. The advantages of this form of treatment over intermittent insulin schedules are emphasized. Early potassium administration, unless otherwise contraindicated, is recommended. Rarely, increasing doses of insulin may be required if insulin resistance is encountered.

Efficacy of low-dose insulin therapy for severely obtunded patients in diabetic ketoacidosis.

To evaluate the efficacy of low-dose insulin therapy in cases of severe diabetic ketoacidosis (DKA), we examined admission clinical and biochemical parameters and responses to therapy in 48 diabetic patients who presented with DKA and were randomized to receive either high- or low-dose insulin. There were no differences in the initial clinical and biochemical parameters of the patients, regardless of assignment to low or high dose; however, a subgroup of 13 patients who were classified as severe DKA (based on their presentation in a comatose or stuporous state) had, as expected, more marked clinical and biochemical abnormalities than their alert cohorts. The responses to therapy (rate of glucose decrement and control of acidosis) were comparable in the high-dose and low-dose groups of comatose/stuporous patients and were not significantly different from the noncomatose cohorts. These data indicate that low-dose insulin therapy in severely ill comatose patients is as effective as high-dose.

Optimal insulin delivery in diabetic ketoacidosis (DKA) and hyperglycemic, hyperosmolar nonketotic coma (HHNC).

Both diabetic ketoacidosis (DKA) and hyperglycemic, hyperosmolar nonketotic coma (HHNC) are stressful metabolic occurrences brought about by the orchestration of numerous events. Adequate hydration and replacement of electrolytes, along with physiologic doses of insulin, are treatment objectives for both of these conditions. Additionally, the physician must search for the factors precipitating these events and frequently evaluate the patient's overall condition.

Nonketotic hyperosmolal diabetic coma in a child: management with low-dose insulin infusion and intracranial pressure monitoring.

Nonketotic hyperosmolal diabetic coma, which is rare in children, is associated with a high mortality in both children and adults. We report a case of nonketotic hyperosmolal diabetic coma in a 3 1/2-year-old child, who was successfully managed with low-dose insulin infusion and invasive intracranial pressure monitoring and recovered without sequelae. Despite severely elevated serum glucose (2,660 mg/dL) and osmolality (435 mosm/kg) levels, there was no elevation of intracranial pressure during her treatment. This case illustrates that insulin should be used cautiously and at low dose in this disease, and that intracranial pressure monitoring is of use in the management of such patients. The pathogenesis and clinical features of nonketotic hyperosmolal diabetic coma are briefly reviewed.

Neurologic manifestations of diabetic comas: correlation with biochemical alterations in the brain.

Coma and other neurologic abnormalities are present in patients with either diabetic ketoacidosis (DKA) or nonketotic coma (NKC), and the cause of such phenomena are not known. Patients with NKC also manifest seizures and focal neurologic changes. Treatment of diabetic coma with insulin may induce cerebral edema by as yet undefined mechanism(s). In patients with DKA, cerebral oxygen utilization is impaired, and there is hyperviscosity of the blood. A substantial part of the brain's energy source is derived from ketones, which in themselves can depress sensorium. Extracellular hyperosomolality is present, which may also contribute to the genesis of coma. In addition, most ketoacidotic patients have associated medical conditions, which may further impair consciousness. Biochemical changes in the brains of animals with DKA include impairment of both phosphofructokinase activity and pyruvate oxidation, and accumulation of citrate. The net effect upon sensorium in ketoacidotic patients probably represents the interaction of most of the above factors and differs markedly among individuals. Patients with NKC manifest not only depression of sensorium, but also focal motor seizures, hemiparesis, and other neurologic changes, such as aphasia, hypereflexia, sensory defects, autonomic changes, and brainstem dysfunction. Most of the aforementioned changes revert to normal after correction of hyperosomolality. Gamma amino butyric acid, which has been shown to elevate the seizure threshold, is normal in brains of ketoacidotic animals, but may be low in nonketotic coma. Also, hyperosomolality per se may produce seizures. Cerebral edema may complicate the treatment of either DKA or NKC. The available experimental evidence suggests that many of the commonly held theories for the production of such brain swelling probably do not occur. There is no breakdown of the sodium pump, sorbitol or fructose do not accumulate in brain, and brain glucose is only about 25 percent of that in plasma; Cerebral edema is probably produced largely by a direct action of insulin on brain at a time when plasma glucose is approaching normal values. Cerebral edema can thus theoretically be avoided by stopping insulin when plasma glucose has been lowered to values approaching normal.

Diabetic ketoacidosis and hyperosmolar hyperglycemic nonketotic coma.

Diabetic ketoacidosis and hyperosmolar hyperglycemic nonketotic coma are two of the most common acute complications of diabetes. The pathophysiologic changes that occur in both disease states represent an extreme example of the super-fasted state. The physiology of the fed and fasted state, evaluation, therapeutic issues, recommendations for therapy, immediate follow up care, and complications of therapy are reviewed for both syndromes.

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.

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.

[Non-ketosic hyperosmolar hyperglycemic coma. Case reports and therapeutic consideration]. / Il coma iperglicemico iperosmolare non chetosico. Contributo casistico e considerazioni terapeutiche

Non-ketonic hyperosmolar hyperglycaemic coma (N.K.H.H.C.) is by no means uncommon in diabetes. Its picture includes sensorial depression, hyperglycaemia, hyperazotemia, marked dehydration and plasma hyperosmolarity. It is mostly found in elderly subjects with non-serious diabetes. Reference is made to 6 personal cases observed during a period of 14 months. The incidence of N.K.H.H.C. noted during this period was 2.2%; this was higher than that of ketoacidotic coma. Two patients died from hypovolaemic shock and one from septic complications. Three survived the episode. Treatment was based on three main points: high doses of insulin, though less than those employed for equal blood sugar levels in cases of ketoacidotic coma, hypotonic saline solutions, and correction of electrolyte imbalance. It is hoped that improved knowledge of the syndrome and, more particularly, earlier diagnosis and treatment, with lead to a reduction in the ta 50% mortality present associated with the disease.

[Low-dose dopamine treatment of patients in nonketotic hyperosmolar hyperglycemic coma].

In the acute neurosurgical setting, nonketotic hyperosmolar hyperglycemic coma (NHC) is thought to be caused by cerebral dehydration therapy and administration of steroids, glycerol, or mannitol. The mortality of this complication is reportedly very high, and is due to acute renal and/or cardiac failure. The authors evaluated the effect of low-dose dopamine (LDD; 1 to 5 micrograms/kg/min) administration in 10 patients with this syndrome. LDD was given to five patients. In these cases, hypovolemia was treated under central venous pressure monitoring with an iso-osmolar hyponatremic lactate solution given in a volume greater than the urine output. After the hypovolemia was corrected, the fluid was administered in a volume equal to the urine output until the serum osmolarity was normalized. In the five patients not given LDD, a large quantity of hypotonic solution was rapidly administered. In all patients treated with LDD, the urinary sodium increased and the urinary output stabilized. Consequently, the excess urea-nitrogen and serum sodium were quite easily washed out. The total net intake volume for the normalization of serum osmolarity was small and the duration of treatment was much shorter than that of patients not treated with LDD. The LDD regimen was not associated with complications, such as aggravation of cerebral edema, renal failure, or cardiac failure. On the other hand, three of the five patients not given LDD died of acute renal and/or cardiac failure without normalization of laboratory data. It is emphasized that this therapy, which results in beta-effect of catecholamine, sodium diuresis, and increased renal blood flow, is a practical means of managing acute neurosurgical cases complicated by NHC.

Treatment of diabetic coma in a tropical environment.

Fourteen patients admitted to Muhimbili Medical Centre, Dar es Salaam in diabetic coma were treated according to a management plan based on the hourly administration of low doses of soluble insulin. The use of this treatment plan resulted in a significant fall in mortality. Three patients died. While these results are still unsatisfactory, the study has shown that combining the treatment plan with enthusiastic and constant medical and nursing care, the results of treatment of diabetic coma in the tropics can approach those of the developed world. The treatment plan is described in detail, since we believe that it can be used in hospitals with only basic facilities.

[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.

Diabetes in children.

Juvenile diabetics comprise approximately five per cent of the total diabetic population. The sex incidence in children is approximately equal and it can occur at any age. However, it would seem that the peak ages for its onset in childhood are between eight and twelve years.