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Defective Glucose Homeostasis in Old People: Ethiopathology and preventive strategies Torna agli editoriali

Anna Giulia Cattaneo, M.D.

Impaired glucose homeostasis plays a role of importance in aged individuals, its manifestations varying from light, often unrecognized hyperglycemia, up to one of most frequent causes of hospital admission and even as a mortality predictive value after stroke or acute cardiac ischemia. Not only higher glycemic values, but even more dangerous hypoglycemic episodes can disturb the frail equilibrium of older patients. The aim of this work is to point out the importance, for the primary care physician and for the taking care of such subjects, to prevent major hypo-or hyperglycemic episodes, and to recognize the co-occurring risk factors that warrant aggressive intervention.

Despite of extremely simple counteracting measures, the ethiopathogenesis of this phenomenon and prediction of its subsequent evolution is a troubleshoot for the physician, who must choice between a cautious waiting for an eventual impairement and shift into pathological conditions, or a series of diagnostic choices that could be time- and money-consuming, disturbing for the frail equilibrium of the aged patient and often frustrating. Knowledge of main events associated to hyperglycemia development and their frequence in the elderly should be of good help in prevention.

Diagnosis of hyperglycemia in the elderly and its predictive value.

The high prevalence of accidental hyperglycemia, impaired glucose tolerance and even diabetes mellitus in old subjects are so widely experienced, that age-adjusted laboratory reference values for basal or loaded glycemia have been early introduced into practice. When the occurrence of hyperglycemia has been detected and confirmed, first and main attention should be payed to the possibility of a so called iatrogenic diabetes. The number of drugs possibly responsible for hyperglycemia is very wide, including many among those commonly used in the elderly, like some hypertensive, diuretics, hypnotics, antidepressant or antipshycotic, analgesic and antirheumatic agents. Every times hyperglycemia occurs the entire therapy should be reconsidered, and a careful anamnestic query for automedication should be done, the defect being reverted simply by removing the not tolerated drug.

On the contrary and despite of the simplicity of tests required to ascertain its presence, hyperglycemia due to type II diabetes remains frequently unrecognized: it has been estimated that in a large managed care organization located in USA, as many as 18% of patients having laboratory fingerprinting for diabetes remains undiagnosed (Edelman D.,Eff. Clin.Pract. 2002, 5, 11-16).
Because of its high risk for complications at the cardiac and vascular, renal, ocular and horthopedic (diabetic foot development) level, early diagnosis and care are recommended. The use of simple risk score based on data commonly available in the primary care and related to the HbA1 levels has been proposed by Meigs JB et al. (Diabetes Care 2002, 25, 977-983). The metabolic or X-syndrome, as defined by the World Ealth Organization is the association of overweight, hypertension, diabetes and hyperlipidemia. It is highly prevalent in general population, even more in the older subjects, and strictly associated to a risk for cardiovascular disease (CVD).(Meigs JB., Am.J.Manag.Care , 2002, 8, S283-292). This syndrome seems to associate main risk factors for developing type II diabetes, that can be divided into two groups: the primary ones, like obesity, age, number of pregnancy, genetic background and the secondary ones, namely hyperinsulinemia, hyperglycemia, dyslipidemia, hypertension. The most predictive for the development of diabetes appear to be obesity and hyperinsulinemia.

Hyperglycemia may develop or worse at the onset of acute stroke and myocardial infarct: in both cases its severity is a predictor of mortality at the short-as well long-course, expecially if not adequately treated at the time of the acute event.
Instead, only a minor role should be abscribed to endocrine pathologies associated with hyperglycemia, whose prevalence is low in the old people, even lower than in the younger or in the middle aged..

Hypoglycemic risk in the elderly.

Hypoglycemia accounts for a relatively high number of emergency requiring hospital admission: it occurs by far more frequently as a consequence of unadequate therapy in diabetes management. The role of hypoglycemia in disturbing the frail homeosthasis of the aged body should be underlined, because of the longer survival of aged people, namely of those affected by various chronic pathologies included diabetes and impaired liver function, made by far more frequent the observation of iatrogenic hypoglycemic insults. The diffuse hypothesis that the the majority, if not all cases of diabetes in the aged should be classified as the non-insulin requiring, or type II diabetes mellitus, should be revisited in the light of general amelioration of geriatric care and frequent observation of cases of insulin-dependent diabetes mellitus in the old and very old. If this phenomenon should be abscribed to a shift from type II to true type I diabetes, or if a reclassification of the entire syndrome should be mandatory, is obviously not the question of this rapid review, but may only be the result of improved ethiopatologic knowledges.
To prevent severe if not even fatal hypoglycemia in old patients, a careful insulin scheduling, when necessary, should include preparations characterized by shorter half-life and minimal risk for nocturnal episodes. The short half-life sulfamides, and molecules tolerated in renal and liver function impairement should be of first choice for geriatric care. Administration of drugs to reduce lipidemia associated to hypoglycemic drugs should be carefully done, because of the possibility of suddenly lowering of glycemic values.
Apart from drug-induced hypoglycemia, most frequent causes of this kind of emergency in the aged are serious hepatic damage, like in ethylic cyrrosis, and paraneoplastic syndromes or metastatic tumors of the adrenal. In these cases, hypoglycemia could develop rapidly and severe enough to reach the convulsive level before any counteraction is adopted, if the event has not been expected and planned in advance. In chronic liver diseases glucose homeostasis is disturbed in a complex way, and both hper- or hypoglycemia could be observed, in relation to the entity of the parenchimal damage, glycogen storage ability and enzymatic function of the residual liver. In particular, hypoglycemia is not usually so severe and frequent in hepatopathies other than ethylic cyrrosis: however in a near future, when a number of survivors to drug abuse should enter in the geriatric condition, a shift of this problem, eventually associated with chronic hepathitis B or with direct drug toxicity, could be observed. In survivors from HIV infection adrenal impairement should be expected (Gonzales-Gonzales JG, Int.I.STD AIDS 2001, 12, 804-810).
The third more frequent cause of hypoglycemia, the panhypopituitarism due to the Sheenan syndrome, is out of geriatric implicances.

Preventive strategies

In many cases the alteration of charbohydrate metabolism found in elderly patients is so light that pharmacological care is probably pleonastic: a cautious behaviour based on moderate prevention is usually the only required intervention. Classical measures adopted in these events are based on dietary counseling, encouraged physical activity, moderate consumption of alchoolics and fats, and a more frequent control of glycemic values, eventually with the addition of postprandial values and glycated hemoglobin testing. An additive precaution could be the hormonal replacement for postmenopausal women.

The prevention of all aging-related disturbances and diseases could be a frustrating thing if the problem is posed, as frequently done, when the aging process has reached its advanced phases: in this case the only prevention appears to be the preservation, as long as possible of affected functions from rapid deterioration. The ideal prevention should involve early detection and removal, if possible, of risk factors in the young, education to safe life and periodic control of principal parameters diagnostic for the most probable pathologies, adjusted for age, sex, and personal features. The ideal is never or quite never realised in the human experience: for this reason the taking-care must be able to make compromises.
In the particular case of hyperglycemic syndromes, the current opinion is that optimal prevention of development or further impairement of hyperglycemic syndromes is based on obesity avoidance or reduction, careful and moderate control of glycemic levels by means of dietary measures and exercise, and control of hypertension and dislipidemia (so called X-syndrome). This is true in the old as well in the younger people, and the apparent simplicity of preventive measures should be priced by a very low number of escaping cases. The contrary is the true: therefore two possibilities can be taken into account. The one is that preventive measures have minor efficacy that postulated on the basis of results of defectively-planned trials. The other that not avoidable factors, like genetic congenital or acquired damage, specific life span with its consequences, or not modifiable aggressive ambient conditions are palying a role.

More simple could be to limit the efforts to care the present conditions. In old people, insulin requirement is generally limited to final phases of their pancreatic defect, and develops late or very late in life. A good control is generally reached by a cautious use of perpherically-acting hypoglycemic agents, like biguanides, sometimes in association with sulphanylureas. It is mandatory for the counselor and for the taking care to take into the mind and prevent the possibilities of lactic acidosis, evenience possible with the first type of drug, and of severe, if not fatal hypoglycemic events, with the second. These eveniences are very dangerous because of the frailty of the aged body, and their occurrence is frequent enough to be very widely known among people devoid to the care of these patients, even if not specialists. Their prevention is based on frequent detection of principal parameters for lactacidemia, avoidance of use of drugs with higher toxic potential, like fenfluramine, and the preference for molecules more tolerated, like the analogous metformine; use of molecules with shorter life, well metabolized by the aged in which some degree of renal impairement is often seen. In old people with cardiac damage or impairement the use of biguanides should be avioded, and the preference given, if prudent, to a cautious therapy with insulin. Accurate education of people living with the patients is very important, whithout dangerous overoptimism or imprudent behaviour: light stress is a good price for a correct prevention of hypoglycemic episodes, potentially destructives. Attention should be payed by the therapist in choicing associated therapy, eventually required for control of hypertension or any other coexhisting condition.
The prevention of alchoolic cyrrosis is only based on very early prevention of alchool continuative abuse, the same is true for hepatic diseases due or associated to hazardous behaviour , like drug or B-hepatitis in drug abusers. The difficulties to succed in this type of prevention are intuitive, and in my opinion more linked to question of crime prevention that to true sanitary problems: the role of the physician should be restaured and limited to the intervention on the organ failure and its consequences.

When considering instead the hypoglycemic events, diverse consideration should be made. In the case of hypoglycemic consequences of inadequate therapy, it can generally be successfully changed, with or whitout specialistic aid, and minor modifications of the actual therapy, or a new, well planned therapeutic strategy. The hypoglycemic spontaneous events observed in cyrrosis or occuring in neoplastic patients can be instead dramatic and unexpected events, at least in their beginning. General conditions of cyrrotic, hypoglycemic prone subjects are often very compromised, and even near the exitus, exspecially in the case of older people. The social background of these subjects is frequently refractory to any serious plane for prevention, sometimes for cure too, and istitutionalitation is frequently required. Finally, the hypoglycemic episodes linked to paraneoplastic syndromes and metastatic tumors are usually acute and even dramatic in their beginning, when they start unespectedly in an environment frequently characterized by stressed emotive reactions. People living with the patients and taking care of him should be trained to recognize and promptly counteract these eveniences, that can start in an early phase of the disaese and occur many times. The rarity of neoplastic syndromes associated with hypoglycemic events is partially counteracted by the relatively higher frequency of neoplasia in the elderly, expecially of type more frequently causing hypoglycemia, like mesotheliomas, microcytomas or tumor of enterochromoaffin cells.

Final considerations

The alterations of glucose metabolism frequent in the elderly can be due to a primary disease, or be secondary to other pathological conditions or to pharmacological or toxic agents. No one of these condition is restricted to the old, but all are common to the adult age and share the same ethiological and diagnostic features. Even prevention and cure are similar, the only true difference being the higher frequence of altered homeostasis and the more severe consequences of a bad care, linked to the fail of counteracting mechanism in the older. Special attention should be payed to the consequences of hypoglycemic events at the cardiac and cerebral level: both organs are particularly frail in the elderly, and the evenience of an acute myocardial infarct or of irreversible cerebral damage subsequent to the insult should be possible

More readings on this subject

  1. 1. Alix M. Diabetes in the elderly patient. Presse Med (2000), 29, 2150-2155 (in French)
  2. Bolk J, van der Ploeg T, Cornel JH, Arnold AE, Sepers AE, Umans VA. Impaired glucose metabolism predicts mortality after a myocardial infarction. Int J Cardiol (2001), 79, 207-214
  3. Dexler AJ, Robertson C. Type 2 diabetes. How new insights, new drugs are changing clinical practice. Geriatrics (2001) 56, 32-33
  4. Edelman D. Outpatient diagnostic errors: unrecognized hyperglycemia.
  5. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination survey. JAMA (2002) 287, 356-359
  6. Holstein A, Plaschke A, Egberts EH. Lower incidence of severe hypoglycemia in patients with type 2 diabetes treated with glimepiride versus glibenclamide. Diabetes Metab Res Rev (2001), 17, 467-473
  7. Imazu M, Sumii K, Yamamoto H, Toyofuku M, Tadehara F, Okubo M, Kohno N, Onaka At, Hawaii-Los Angeles- Hiroshima study. Diabetes Res Clin Pract. (2002), 57, 61-69
  8. Koller E, Schneider B, Bennett K, Dubitsky G. Clozapine-associated diabetes. Am J Med (2001), 111, 716-723
  9. Lai SW, Li TC, Ng KC. Body mass index and its related factors in the elderly. Ann Acad Med Singapore (2001), 30, 397-400
  10. Lindenmayer JP, Nathan AM, Smith RC. Hyperglycemia associated with the use of atypical antipsychotics. J Clin Psichiatry (2001), 62 suppl. 23, 30-38
  11. Meigs JB. Epidemiology of the metabolic syndrome, 2002. Am J Manag Care (2002), 8 suppl 11, S283-292
  12. Resnick He, Shorr RI, Kuller L, Franse L, Harris TB. Prevalence and clinical implications of American Diabetes Association-defined diabetes and other categories of glucose dysregulation in older adults: the health, aging and body composition study. J Clin Epidemiol (20019, 54, 869-876
  13. Sthal M, Berger W. Higher incidence of severe hypoglycaemia leading to hospital admission in Type 2 diabetic patients treated with long-acting versus short-acting sulphonylureas. Diabet Med (1999), 16, 586-590
  14. Vauzelle-Kervoroedan F, Delcourt C, Forhan A, Jougla E, Hatton F, Papoz L. Analysis of mortality in French diabetic patients from death certificates : a comparative study. Diabetes Metab (1999), 25, 404-411
  15. Williams LS, Rotich J, Qi R, Fineberg N, Espay A, Bruno A, Fineberg SE, Tierney WR. Effects of admission hyperglycemia on mortality and costs in acute ischemic stroke. Neurology (2002), 59, 67-71

Department of Structural and Functional Biology, Insubrian University, Via J.H.Dunant, 3, 21100 Varese, Italy

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