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Plasma insulin response to oral glucose load in Ménière's disease
Am J Otolaryn8ol 7:250-252, 1986
Plasma Insulin Response to Oral Glucose Load in M ni re's Disease S. KARJALAINEN,M.D., H. SARLUND,M.D., E. VARTIAINEN,M.D., AND K. PYORALA,M.D. Oral glucose tolerance tests and plasma insulin measurements were carried out in 74 patients with M~niere's disease and 74 control subjects. No statistically significant differences were observed in fasting, one-hour, and two-hour blood glucose levels or in fasting, one-hour, and two-hour plasma insulin levels between patients with Meniere's disease and control subjects. The results do not confirm the hypothesis that disturbances in glucose metabolism or plasma insulin response are etiologic factors in M~niere's disease.
Many authors are currently of the view that M~ni~re's disease is not a single entity but embraces a number of disorders with similar aural manifestations. Metabolic disorders are known to affect inner ear function. However, estimates of their prevalence in M~ni~re's disease has varied greatly in different studies. 1-8 UpdegrafO and Proctor et al. 7 have postulated that impairment of glucose metabolism or abnormalities in plasma insulin response to glucose challenge are common in patients with M6ni~re's disease and that such disturbances are important and often overlooked causes of vertigo. In a previous study, 9 we found no differences in glucose or lipid metabolism in patients with M~ni~re's disease as compared with glucose or lipid metabolism in patients with otosclerosis. In that study, however, no plasma insulin measurements were carried out. We have now performed a study on glucose metabolism in patients with M~ni~re's disease in which plasma insulin levels were m e a s u r e d in connection with oral glucose tolerance testing (OGTT).
SUBJECTS AND METHODS
on glucose and lipid metabolism in patients exhibiting M6ni~re's symptom complex. 9 The 81 patients participating in that study were recalled for repetition of OGTT and m e a s u r e m e n t of plasma insulin levels. Patients with previously diagnosed diabetes mellitus (two cases) or impaired glucose tolerance (four cases) were excluded. Fifty patients were re-examined. In addition, we included in the series 24 new, consecutive patients with M~ni~re's disease. Thus, the number of patients with M~ni~re's disease in the present study was 74. Otoneurological evaluation confirmed bilateral M~ni~re's disease in 11 cases. Twenty-eight of the patients (38 per cent) were men (mean age 49.7 years, range 27 to 69 years) and 46 were women (62 per cent) (mean age 51.9 years, range 34 to 68 years). A case-control study design was used. Control subjects were healthy subjects who had participated in a family study on determinants of glucose tolerance, plasma insulin levels, and lipid metabolism. The 74 control subjects were m a t c h e d according to sex and age with the patients with
A description of the methods used to define M~ni~re's disease has been given in our report
TABLE 1. Fifth and 95th Percentiles of Plasma Insulin Levels in Reference Population (N = 271)
Received February 11, 1986, from the Departments of Otolaryngology and Medicine, Kuopio University Central Hospital, Kuopio, Finland. Accepted for publication March 19, 1986. Address reprint requests to Dr. Karjalainen: Department of Otolaryngology, University of Kuopio, SF-70210 Kuopio, Finland. 0196-0709/86 $00.00 + .25
INSULIN
Fasting One-hour Two-hour
250
(mIU/l)
5th percentile
95th percentile
5.4 25.8 12.4
23.4 183.1 123.1
KARAJALAINEN El' AL.
TABLE 2.
Blood Glucose and Plasma Insulin Levels in Patients with MO.nib.re's Disease and Control Subjects CONTROLS
MI~NIERE'S DISEASE (N = 74)
(N = 74)
Mean
SD
Mean
4.2 6.5 4.8
0.8 2.2 1.3
4.6 6.2 5.2
SD
Blond glucose (mmol/l} Fasting One-hour Two-hour
0.7 2.2 1.8
Plasma insulin (mIU/1) Fasting
11.2
5.6
11.3
5.7
One-hour
82.9
51.9
69.4
59.0
Two-hour
54.0
51.2
49.0
57.9
M6ni6re's disease. None of the controls had been p r e v i o u s l y diagnosed as suffering from diabetes, coronary artery disease, marked obesity, or any other condition that could have affected plasma insulin levels. The OGTT was performed in the morning, after subjects had fasted for at least 12 hours. The glucose dose was 75 g in a 10 per cent solution. Venous blood samples for blood glucose and plasma insulin measurements were taken before glucose loading and one and two hours thereafter. Plasma insulin levels were determined using a commercial double antibody radioimmunoassay kit. In control subjects who had participated in the family study mentioned previously, plasma glucose rather than whole blood glucose had been measured, and a factor of 0.87 (plasma values being 15 per cent greater than whole blood values) was used to convert the plasma glucose values to the corresponding blood glucose values. Fasting whole blood glucose (FWBG) values of over 7.0 mmol/liter and/or two-hour OGTT WBG values of over 10.0 mmol/liter were regarded as diagnostic of diabetes mellitus. 10 Any FWBG values below 7.0 mmol/1 and two-hour OGTT
TABLE 3. Categorization of Patients with Mdni6re's Disease and Controls in Low and High Plasma Insulin Classes* MI~NIF.RE'S D I S E A S E (N = 74) Fasting ~<5th >95th
CONTROLS
(N = 74)
9 2
5 1
10 5
3 3
One-hour ~<5th >95th
Two-hour ~<5th
7
2
>95th
3
4
* On the basis of the 5th and 95th percentiles of plasma insulin levels in the reference population.
WBG values of between 7.0 and 10.0 mmol/1 were regarded as indicative of impaired glucose tolerance. '1 The corresponding plasma glucose (PG) values for diabetes mellitus were over 8.0 mmol/1 (FPG) and/or over 11.0 mmol/1 (two-hour OGTT PG). In the case of impaired glucose tolerance, the corresponding PG values were less than 8.0 mmol (FPG) and between 8.0 and 11.0 mmol/1 (two-hour OGTT PG). The 5th and 95th percentiles for plasma insulin variables were computed for a reference population of 271 healthy subjects participating in the family study. These percentile values were used in categorizing patients with M6ni6re's d i s e a s e as m e m b e r s of low or high plasma insulin classes (Table 1). Statistical c o m p a r i s o n s b e t w e e n cases and controls were carried out using the t-test for paired comparisons, in relation to continuous variables, and McNemar's test, in relation to class variables.
RESULTS The mean value and standard deviation relating to body mass index for patients with M6ni6re's disease was 25.67 _+ 3.98 kg/m. For controis, the corresponding values were 24.32 +_ 2.07 kg/m (not statistically significant). The mean values and standard deviations for plasma insulin levels are shown in Table 2. There were no statistically significant differences between patients with M6ni6re's disease and control subjects. Five patients with M6ni6re's disease and four control subjects had impaired glucose tolerance on the basis of their two-hour OGTT blood glucose levels. The distribution of patients with M6ni6re's disease and control subjects in relation to the 5th and 95th percentiles of plasma insulin levels in the reference population is shown in Table 3. There was a trend to an excessive occurrence of
Volume 7 Number 4 July 1986 251
PLASMA INSULIN IN MENIERE'S DISEASE
low (~< 5th percentile) plasma insulin levels among patients with M6ni~.re's disease as compared with control subjects, but the difference was not statistically significant.
DISCUSSION Abnormalities in glucose metabolism and plasma insulin responses to glucose challenge in patients with M6ni~re's disease and their possible role in its etiology have recently been the subject of considerable interest and controversy. Proctor et al. 7 observed either abnormal OGTT results or abnormal (high or low) plasma insulin responses in 76 per cent of 50 patients with M6ni~re's disease. Charles et al. 12 reported significantly increased levels of insulin in patients with M6ni~re's disease and recurrent vestibulopathy or psychogenic vertigo. They presumed, however, that the findings reflected differences in age and weight distribution between the case and control groups. In the present study, using a case-control study design, we found no statistically significant differences in blood glucose or plasma insulin levels during OGTT between patients with M6ni~re's disease and control subjects, although there was a trend toward an excessive occurrence of low plasma insulin levels among patients with M6ni6re's disease. On the basis of the results of the present study, we conclude that abnormalities of glucose metabolism and plasma insulin responses to glucose challenge show no clear relationships
American Journal of Otolaryngology 252
to M6ni~re's disease and that screening for those abnormalities is of no importance in the clinical evaluation of patients with M6ni6re's symptom complex.
References 1. Updergraff WR: Impaired carbohydrate metabolism and idiopathic M~ni~re's disease. Ear Nose Throat J 56:160-163, 1977 2. Powers WH: Metabolic aspects of M~ni~re's disease. Laryngoscope 88:122-129, 1978 3. Moffat DA, Booth JB, Morrison AW: Metabolic investigations in M~ni~re's disease. J Laryngol Otol 93:545561, 1979 4. Dolowitz DA: M6ni~re's--an inner ear seizure. Laryngoscope 89:67-77, 1979 5. Kinney SE: The metabolic evaluation in M~ni~re's disease. Otolaryngol Head Neck Surg 88:594-598, 1980 6. Moffat DA, Booth JB, Morrison AW: Metabolic investigations in M~ni~re's disease. J Laryngol Otol 95:905913, 1981 7. Proctor B, Proctor C: Metabolic management in M~nibre's disease. Ann Otol Rhinol Laryngol 90:615618, 1981 8. Meyerhoff WL, Paparella MM, Gudbrandsson FK: Clinical evaluation of M6ni~re's disease. Laryngoscope 91:1663-1668, 1981 9. Karjalainen S, Nuutinen J, K~irj/iJ, et al: Lack of utility of metabolic screening in Meni~.~re's disease. Clin Otolaryngol 9:15-20, 1984 10. World Health Organization: Expert Committee on Diabetes Mellitus. Second Report. WHO Technical Report Series No. 676:1-80, 1980 11. National Diabetes Data Group: Classification and diagnosis of diabetes meltitus and other categories of glucose tolerance. Diabetes 28:1039-1057, 1979 12. Charles DA, Barber HO, Hope-Gill HF: Blood glucose and insulin levels, thyroid function, and serology in M~ni~re's disease, recurrent vestibulopathy, and psychogenic vertigo. J Otolaryngal 8:347-353, 1979
Plasma Insulin Response to Oral Glucose Load in M ni re's Disease S. KARJALAINEN,M.D., H. SARLUND,M.D., E. VARTIAINEN,M.D., AND K. PYORALA,M.D. Oral glucose tolerance tests and plasma insulin measurements were carried out in 74 patients with M~niere's disease and 74 control subjects. No statistically significant differences were observed in fasting, one-hour, and two-hour blood glucose levels or in fasting, one-hour, and two-hour plasma insulin levels between patients with Meniere's disease and control subjects. The results do not confirm the hypothesis that disturbances in glucose metabolism or plasma insulin response are etiologic factors in M~niere's disease.
Many authors are currently of the view that M~ni~re's disease is not a single entity but embraces a number of disorders with similar aural manifestations. Metabolic disorders are known to affect inner ear function. However, estimates of their prevalence in M~ni~re's disease has varied greatly in different studies. 1-8 UpdegrafO and Proctor et al. 7 have postulated that impairment of glucose metabolism or abnormalities in plasma insulin response to glucose challenge are common in patients with M6ni~re's disease and that such disturbances are important and often overlooked causes of vertigo. In a previous study, 9 we found no differences in glucose or lipid metabolism in patients with M~ni~re's disease as compared with glucose or lipid metabolism in patients with otosclerosis. In that study, however, no plasma insulin measurements were carried out. We have now performed a study on glucose metabolism in patients with M~ni~re's disease in which plasma insulin levels were m e a s u r e d in connection with oral glucose tolerance testing (OGTT).
SUBJECTS AND METHODS
on glucose and lipid metabolism in patients exhibiting M6ni~re's symptom complex. 9 The 81 patients participating in that study were recalled for repetition of OGTT and m e a s u r e m e n t of plasma insulin levels. Patients with previously diagnosed diabetes mellitus (two cases) or impaired glucose tolerance (four cases) were excluded. Fifty patients were re-examined. In addition, we included in the series 24 new, consecutive patients with M~ni~re's disease. Thus, the number of patients with M~ni~re's disease in the present study was 74. Otoneurological evaluation confirmed bilateral M~ni~re's disease in 11 cases. Twenty-eight of the patients (38 per cent) were men (mean age 49.7 years, range 27 to 69 years) and 46 were women (62 per cent) (mean age 51.9 years, range 34 to 68 years). A case-control study design was used. Control subjects were healthy subjects who had participated in a family study on determinants of glucose tolerance, plasma insulin levels, and lipid metabolism. The 74 control subjects were m a t c h e d according to sex and age with the patients with
A description of the methods used to define M~ni~re's disease has been given in our report
TABLE 1. Fifth and 95th Percentiles of Plasma Insulin Levels in Reference Population (N = 271)
Received February 11, 1986, from the Departments of Otolaryngology and Medicine, Kuopio University Central Hospital, Kuopio, Finland. Accepted for publication March 19, 1986. Address reprint requests to Dr. Karjalainen: Department of Otolaryngology, University of Kuopio, SF-70210 Kuopio, Finland. 0196-0709/86 $00.00 + .25
INSULIN
Fasting One-hour Two-hour
250
(mIU/l)
5th percentile
95th percentile
5.4 25.8 12.4
23.4 183.1 123.1
KARAJALAINEN El' AL.
TABLE 2.
Blood Glucose and Plasma Insulin Levels in Patients with MO.nib.re's Disease and Control Subjects CONTROLS
MI~NIERE'S DISEASE (N = 74)
(N = 74)
Mean
SD
Mean
4.2 6.5 4.8
0.8 2.2 1.3
4.6 6.2 5.2
SD
Blond glucose (mmol/l} Fasting One-hour Two-hour
0.7 2.2 1.8
Plasma insulin (mIU/1) Fasting
11.2
5.6
11.3
5.7
One-hour
82.9
51.9
69.4
59.0
Two-hour
54.0
51.2
49.0
57.9
M6ni6re's disease. None of the controls had been p r e v i o u s l y diagnosed as suffering from diabetes, coronary artery disease, marked obesity, or any other condition that could have affected plasma insulin levels. The OGTT was performed in the morning, after subjects had fasted for at least 12 hours. The glucose dose was 75 g in a 10 per cent solution. Venous blood samples for blood glucose and plasma insulin measurements were taken before glucose loading and one and two hours thereafter. Plasma insulin levels were determined using a commercial double antibody radioimmunoassay kit. In control subjects who had participated in the family study mentioned previously, plasma glucose rather than whole blood glucose had been measured, and a factor of 0.87 (plasma values being 15 per cent greater than whole blood values) was used to convert the plasma glucose values to the corresponding blood glucose values. Fasting whole blood glucose (FWBG) values of over 7.0 mmol/liter and/or two-hour OGTT WBG values of over 10.0 mmol/liter were regarded as diagnostic of diabetes mellitus. 10 Any FWBG values below 7.0 mmol/1 and two-hour OGTT
TABLE 3. Categorization of Patients with Mdni6re's Disease and Controls in Low and High Plasma Insulin Classes* MI~NIF.RE'S D I S E A S E (N = 74) Fasting ~<5th >95th
CONTROLS
(N = 74)
9 2
5 1
10 5
3 3
One-hour ~<5th >95th
Two-hour ~<5th
7
2
>95th
3
4
* On the basis of the 5th and 95th percentiles of plasma insulin levels in the reference population.
WBG values of between 7.0 and 10.0 mmol/1 were regarded as indicative of impaired glucose tolerance. '1 The corresponding plasma glucose (PG) values for diabetes mellitus were over 8.0 mmol/1 (FPG) and/or over 11.0 mmol/1 (two-hour OGTT PG). In the case of impaired glucose tolerance, the corresponding PG values were less than 8.0 mmol (FPG) and between 8.0 and 11.0 mmol/1 (two-hour OGTT PG). The 5th and 95th percentiles for plasma insulin variables were computed for a reference population of 271 healthy subjects participating in the family study. These percentile values were used in categorizing patients with M6ni6re's d i s e a s e as m e m b e r s of low or high plasma insulin classes (Table 1). Statistical c o m p a r i s o n s b e t w e e n cases and controls were carried out using the t-test for paired comparisons, in relation to continuous variables, and McNemar's test, in relation to class variables.
RESULTS The mean value and standard deviation relating to body mass index for patients with M6ni6re's disease was 25.67 _+ 3.98 kg/m. For controis, the corresponding values were 24.32 +_ 2.07 kg/m (not statistically significant). The mean values and standard deviations for plasma insulin levels are shown in Table 2. There were no statistically significant differences between patients with M6ni6re's disease and control subjects. Five patients with M6ni6re's disease and four control subjects had impaired glucose tolerance on the basis of their two-hour OGTT blood glucose levels. The distribution of patients with M6ni6re's disease and control subjects in relation to the 5th and 95th percentiles of plasma insulin levels in the reference population is shown in Table 3. There was a trend to an excessive occurrence of
Volume 7 Number 4 July 1986 251
PLASMA INSULIN IN MENIERE'S DISEASE
low (~< 5th percentile) plasma insulin levels among patients with M6ni~.re's disease as compared with control subjects, but the difference was not statistically significant.
DISCUSSION Abnormalities in glucose metabolism and plasma insulin responses to glucose challenge in patients with M6ni~re's disease and their possible role in its etiology have recently been the subject of considerable interest and controversy. Proctor et al. 7 observed either abnormal OGTT results or abnormal (high or low) plasma insulin responses in 76 per cent of 50 patients with M6ni~re's disease. Charles et al. 12 reported significantly increased levels of insulin in patients with M6ni~re's disease and recurrent vestibulopathy or psychogenic vertigo. They presumed, however, that the findings reflected differences in age and weight distribution between the case and control groups. In the present study, using a case-control study design, we found no statistically significant differences in blood glucose or plasma insulin levels during OGTT between patients with M6ni~re's disease and control subjects, although there was a trend toward an excessive occurrence of low plasma insulin levels among patients with M6ni6re's disease. On the basis of the results of the present study, we conclude that abnormalities of glucose metabolism and plasma insulin responses to glucose challenge show no clear relationships
American Journal of Otolaryngology 252
to M6ni~re's disease and that screening for those abnormalities is of no importance in the clinical evaluation of patients with M6ni6re's symptom complex.
References 1. Updergraff WR: Impaired carbohydrate metabolism and idiopathic M~ni~re's disease. Ear Nose Throat J 56:160-163, 1977 2. Powers WH: Metabolic aspects of M~ni~re's disease. Laryngoscope 88:122-129, 1978 3. Moffat DA, Booth JB, Morrison AW: Metabolic investigations in M~ni~re's disease. J Laryngol Otol 93:545561, 1979 4. Dolowitz DA: M6ni~re's--an inner ear seizure. Laryngoscope 89:67-77, 1979 5. Kinney SE: The metabolic evaluation in M~ni~re's disease. Otolaryngol Head Neck Surg 88:594-598, 1980 6. Moffat DA, Booth JB, Morrison AW: Metabolic investigations in M~ni~re's disease. J Laryngol Otol 95:905913, 1981 7. Proctor B, Proctor C: Metabolic management in M~nibre's disease. Ann Otol Rhinol Laryngol 90:615618, 1981 8. Meyerhoff WL, Paparella MM, Gudbrandsson FK: Clinical evaluation of M6ni~re's disease. Laryngoscope 91:1663-1668, 1981 9. Karjalainen S, Nuutinen J, K~irj/iJ, et al: Lack of utility of metabolic screening in Meni~.~re's disease. Clin Otolaryngol 9:15-20, 1984 10. World Health Organization: Expert Committee on Diabetes Mellitus. Second Report. WHO Technical Report Series No. 676:1-80, 1980 11. National Diabetes Data Group: Classification and diagnosis of diabetes meltitus and other categories of glucose tolerance. Diabetes 28:1039-1057, 1979 12. Charles DA, Barber HO, Hope-Gill HF: Blood glucose and insulin levels, thyroid function, and serology in M~ni~re's disease, recurrent vestibulopathy, and psychogenic vertigo. J Otolaryngal 8:347-353, 1979