Haemodynamic changes in insulin-induced hypoglycaemia in normal man

Hilsted, J.; Bonde-Petersen, F; Nørgaard, Mie; Greniman, M.; Christensen, Niels Juel; Parving, Hans‐Henrik; Suzuki, Masayasu

doi:10.1007/bf00266031

Cited by 101 publications

(77 citation statements)

References 20 publications

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“…To verify the safety of OHA treatment, blood glucose profiles should be performed in Type 2 diabetic patients; at least a late afternoon value should be regularly checked. The risk of repeated low glucose values must be carefully considered in an older population potentially affected by atherosclerotic lesions, to avoid the iatrogenic effects of neuroglycopoenia and of catecholamine-mediated vascular damage [2][3][4][5][6][7][8][9]. In this light, the fasting and postprandial glycaemic targets of the European Policy Group [1] should be considered in an integrate view, and not separately.…”

Section: Discussionmentioning

confidence: 99%

“…The 4.4 mmol/1 limit is due to the fact that lower concentrations could be dangerous in an older population frequently affected by vasculopathy, since values greater than the limits of chemical hypoglycaemia cause neurological abnormalities due to neuroglycopoenia and activate adrenergic glucose counterregulation [2]. The latter phenomenon is potentially dangerous as it can precipitate vascular complications of the disease owing to haemorheological, haemodynamic and haemostatic changes, as it has been described during insulin-induced hypoglycaemia [3][4][5][6][7][8][9]. Since one of the main targets of Type 2 diabetes treatment is the prevention of angiopathy, it is particularly important to avoid low blood glucose concentrations.…”

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confidence: 99%

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Occurrence of low blood glucose concentrations during the afternoon in Type 2 (non-insulin-dependent) diabetic patients on oral hypoglycaemic agents: importance of blood glucose monitoring

et al. 1991

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Summary.The European NIDDM Policy Group states that the lowest target for good control of Type 2 (non-insulin-dependent) diabetic patients is a blood glucose level 4.4 mmol/1, both fasting and postprandially. The aim of this study is to evaluate the occurrence and temporal distribution of values under this target in the clinical records of 463 Type 2 diabetic patients, treated by diet or diet and oral hypoglycaemic agents, monitored for at least 2 years. The protocol includes blood glucose measurements after overnight fasting (08.00 hours), 120-150 rain after breakfast (11.00 hours) and 120 and 240 min after lunch (14.00 and 16.00 hours). At least one blood glucose concentration of less than 4.4 mmol/1 was presented by 42% of the patients. The only difference between patients showing and not showing glycaemic levels under this target was the higher percentage on oral hypoglycaemic agents in the first group (68.4% vs 56.9% ,p = 0.016). We considered 299 blood glucose profiles containing at least one value of less than 4.4 retool/l, observing that a) 46.9% of profiles from patients treated by diet alone and 68.7% of profiles from patients treated both by diet and oral hypoglycaemic agents presented the lowest blood glucose concentration at 16.00 hours (p = 0.002). b) No correlation existed between fasting blood glucose and values at 16.00 hours in profiles from diet-treated patients, whereas a negative correlation was present in patients on diet and oral hypoglycaemic agents, indicating that an excess of oral agents, administered to correct fasting hyperglycaemia, was the cause of the low glycaemic values in the afternoon, c) 37.9% of profiles on a diet and 83.3% of profiles on diet and oral agents showed fasting glucose concentrations > 6.7 mmol/1, the upper limit of good control according to the European NIDDM Policy Group. This indicates that fasting hyperglycaemia does not exclude the occurrence of low glucose values throughout the day and that it is necessary to monitor blood glucose profiles.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Occurrence of low blood glucose concentrations during the afternoon in Type 2 (non-insulin-dependent) diabetic patients on oral hypoglycaemic agents: importance of blood glucose monitoring

et al. 1991

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“…In one hypoglycemia clamp study (plasma glucose 3.0 mmol/L [54 mg/dL]) in participants without diabetes, a 12-fold increase in plasma epinephrine concentration was observed that was associated with increased heart rate and cardiac stroke volume and decreased peripheral resistance (15). Acute hypoglycemia provokes a substantial rise in myocardial contractility (16) and cardiac output (17). These hemodynamic changes are accompanied by an increase in elasticity of large blood vessels and a fall in central arterial pressure, with both measures being diminished in young men with type 1 diabetes of long duration (.15 years) in whom arterial stiffness has developed (18).…”

Section: Cardiovascular Effects Of Hypoglycemiamentioning

confidence: 99%

Hypoglycemia and Cardiovascular Risk: Is There a Major Link?

2016

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Severe hypoglycemia is recognized to be one of the strongest predictors of macrovascular events, adverse clinical outcomes, and mortality in patients with type 2 diabetes. However, it is uncertain whether a direct pathophysiological link exists or whether hypoglycemia is primarily a marker of vulnerability to these events. Large clinical trials have reported an increased hazard ratio for all-cause mortality and cardiovascular events in patients with type 2 diabetes and severe hypoglycemia, but such an association has not been demonstrated in prospective trials of people with type 1 diabetes. Several cardiovascular effects occur during hypoglycemia either as a result of low blood glucose levels per se or through activation of the sympathoadrenal response: hemodynamic changes with an increase in cardiac work load and potential attenuation of myocardial perfusion, electrophysiological changes that may be arrhythmogenic, induction of a prothrombotic state, and release of inflammatory markers. Although the potential for a causal relationship has been demonstrated in mechanistic studies, the evidence from large prospective studies that hypoglycemia is a major causal contributor to cardiovascular events is limited to date. Other preexisting cardiovascular risk factors in addition to hypoglycemia may be the major link to the final cardiovascular event, but a low blood glucose level can trigger these events in patients with a high cardiovascular risk.

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“…8 -10 These observations have supported the suggestion that the tachycardia and the rise in blood pressure observed during a hypoglycemic episode might destabilize an atherosclerotic plaque. 11 These hemodynamic changes, the increased myocardial work, and hypoglycemia-induced increases in platelet aggregation, platelet activity, [12][13][14] and hematocrit 15,16 may precipitate cardiac and cerebral ischemic events in patients at high risk of cardiovascular disease. 17 Support for this possibility comes from a number of small studies and case reports.…”

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confidence: 99%

Serious Cardiovascular Outcomes in Diabetes

Yakubovich

Gerstein

2011

Circulation

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H ypoglycemia is a well-recognized side effect of glucoselowering therapies in patients with diabetes mellitus. The incidence of mild self-reported hypoglycemic episodes in patients with type 1 diabetes mellitus is approximately 30 episodes per patient per year, whereas the incidence of severe hypoglycemic episodes (ie, those that require third-party assistance) may be as high as 3.2 episodes per patient per year. 1-3 Hypoglycemic episodes occur much less frequently in patients with type 2 diabetes mellitus, in whom the incidence of mild and severe hypoglycemic episodes is 2 to 10 per patient per year and 0.1 to 0.7 per patient per year, respectively. 2 When patients are alerted to the occurrence of a hypoglycemic episode by symptoms such as tremor, diaphoresis, tachycardia, malaise, hunger, and anxiety, they can abort these episodes by consuming carbohydrates. However, if hypoglycemic episodes occur rapidly or are unrecognized and untreated, the resulting neuroglycopenia may cause confusion, seizures, accidents, angina, and, rarely, death or permanent cognitive impairment. 3,4 Patients who experience frequent episodes of hypoglycemia are especially at risk of having unrecognized hypoglycemic episodes (and their sequelae), because their counterregulatory response to hypoglycemia becomes blunted. Indeed, the rare occurrence of sudden death during sleep in young patients with type 1 diabetes mellitus (the so-called dead-in-bed syndrome) has been attributed to hypoglycemia, although this cause is seldom proven. [5][6][7] It is well known that hypoglycemic episodes are associated with a surge of sympathetic activity and a release of catecholamines. 8 -10 These observations have supported the suggestion that the tachycardia and the rise in blood pressure observed during a hypoglycemic episode might destabilize an atherosclerotic plaque. 11 These hemodynamic changes, the increased myocardial work, and hypoglycemia-induced increases in platelet aggregation, platelet activity, 12-14 and hematocrit 15,16 may precipitate cardiac and cerebral ischemic events in patients at high risk of cardiovascular disease. 17 Support for this possibility comes from a number of small studies and case reports. For example, continuous glucose and ECG monitoring in 19 patients with coronary artery disease and type 2 diabetes mellitus 18 revealed a higher frequency of ischemic ECG changes when glucose levels fell below 3.9 mmol/L (70 mg/dL). A similar study in 24 patients with type 1 diabetes mellitus 19 revealed a nocturnal increase in the corrected QT interval and some minor rhythm disturbances when nocturnal glucose levels fell below 3.5 mmol/L (63 mg/dL) that were not observed when nocturnal glucose levels were Ͼ5 mmol/L (90 mg/dL). Experimentally induced hypoglycemia prolonged the corrected QT interval and reduced potassium levels in healthy adults 10 and in people with type 1 and type 2 diabetes mellitus. 20,21 Finally, case reports have shown a relationship between ischemic cerebral changes and concurrent severe hypoglycemia in patie...

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Haemodynamic changes in insulin-induced hypoglycaemia in normal man

Cited by 101 publications

References 20 publications

Occurrence of low blood glucose concentrations during the afternoon in Type 2 (non-insulin-dependent) diabetic patients on oral hypoglycaemic agents: importance of blood glucose monitoring

Occurrence of low blood glucose concentrations during the afternoon in Type 2 (non-insulin-dependent) diabetic patients on oral hypoglycaemic agents: importance of blood glucose monitoring

Hypoglycemia and Cardiovascular Risk: Is There a Major Link?

Serious Cardiovascular Outcomes in Diabetes

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