You are on page 1of 6

A new pharmacologic agent, possible to be used in reducing insulin resistance

T. MOGOŞ, ANDRA IACOBINI, CLAUDIA-VALERIA CHELAN

“Prof. Dr. N.C. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases

Insulin resistance is the cornerstone of multiple diseases such as metabolic syndrome, diabetes mellitus, arterial hypertension, dyslipidemia, acute coronary syndrome, etc. There are some medications and changes in lifestyle that can reduce insulin resistance. Not all are suitable for all patients. We discovered another pharmacologic agent that can be successfu lly added to the old methods already in use.

Key words: insulin resistance, Gerovital® H3 , metabolic syndrome.

Insulin resistance (IR) is one of the corner- stones of several syndromes with large impact on arterial diseases: metabolic syndrome, diabetes mellitus, hypertension, acute coronary syndrome, etc. [1,4]. There are a lot of known methods that reduce IR, but their efficiency is not always long-lasting and not so powerful for every product [3]. That is why in the treatment of IR we combine different methods adapted to every patient’s needs, in order to obtain the maximum benefit for the individual therapy [3,4]. The methods of reducing IR include weight loss, physical activity, medication (metformin, pioglitazone), correction of hyperglycemia, hyper- natremia, hyperlipidemia, etc. [2,5]. As we already mentioned, depending on the present factors that increase IR, we adapt the therapy to every patient’s needs. Unfortunately, there are a lot of other not yet identified factors that make IR present and capable of inducing dysfunction or atherosclerosis of the arterial vessels [11]. As a result of an extensive experience in the field of IR, we observed that this phenomenon can also be reduced by other methods. One of them was far more efficient compared with the others. It is a product with an international name (Gerovital ® H3 ) usually used in geriatric medicine. We observed that this pharmacologic agent improves insulin sen- sitivity, not only in the insulin-treated patients. We administered 10 mL of this substance by i.m. injection every day, for the period taken in observation.

ROM. J. INTERN. MED., 2014, 52, 4, 233–238

MATERIALS AND METHODS

Our study was carried out on 416 patients with IR. We analyzed them from January 2013 until September 2014. Most of the subjects were females (215), the rest being males (201). From the female group, 54 had diabetes mellitus and from the male group, 32 suffered from diabetes. These patients have been separately analyzed in a particular way, as we will later show. The other IR patients were not separately analyzed because a part of their conditions were not connected with our field of medicine. Among those investigated, the duration of IR was unknown, but we did know the duration of the syndromes that can associate with IR: for metabolic syndrome (11 ± 2 years), for diabetes mellitus (9 ± 3 years), hypertension (14 ± 4 years), acute coronary syndromes (7 ± 2 years). The patients’ average age was 54 ± 11 years (58 ± 12 years for women; 50 ± 11.2 years for men). The mean BMI was 28.9 ± 1.5 kg/m 2 in the male group and 30.2 ± 1.8 kg/m 2 in the female group, with a reduced statistical difference (p <

0.05).

We determined each subject’s IR using the HOMA method. For the insulin-treated group we measured the daily insulin requirement at the beginning of treatment and after treatment with Gerovital ® H3 (2 weeks). For the rest of the patients, we determined HOMA-IR at the beginning and

234

T. Mogoş et al.

2

after 2 weeks of treatment. The glycemic values were evaluated by blood sugar samples using the Accu-Chek Active ®. We stress that none of the patients received any education regarding lifestyle changes and did not have any other factors (such as medication) that could influence their IR. For a selected group of 10 subjects we extended the treatment for another week.

RESULTS

The parameters of IR, for all patients taken in observation, associated or not with the syndromes usually depending on IR, indicated at the beginning of the study a value for HOMA-IR of 2.8 ± 0.5 for the male group and of 3.1 ± 0.8 for the female group (p < 0.001). As we already mentioned, following a 2 weeks treatment with Gerovital ® H3 , the value of HOMA-IR for the male group unexpectedly decreased from 2.8 ± 0.5 to 2.5 ± 0.4 and in the female group from 3.1 ± 0.8 to 2.6 ± 0.9 (p < 0.001). For the rest of the patients that did not receive this treatment, there was no decrease in IR, which could have a negative impact on healthcare. In Figure 1 and Figure 2 we illustrate the difference between the two levels of IR, at the beginning and after 2 weeks of treatment, in the female vs. the male group.

As we already mentioned, for the 10 subjects (5 males and 5 females), the period of Gerovital ® H3 injection was prolonged for another week. As a male group (Figure 4) from 2.8 ± 0.5 to 2.3 ± 0.4. These results show us that treatment over longer periods of time further decreases IR (Figure 5 and Figure 6). The IR decrease is maintained about three weeks after the end of 2 weeks of treatment and lasts for more than 25 days after 3 weeks of treatment. As we mentioned above, for the subjects with IR that associated diabetes mellitus we measured the total daily requirements at the beginning and at the end of the two weeks of treatment and also the mean blood sugar at the start and at the end of the study. At the beginning of the study, the mean glycemia in the male group was 168.5 ± 12 mg/dL, respectively174.4 ± 11.6 mg/dL for the female group (p < 0.001). The total daily insulin require- ment for the male group was 34.5 ± 8 units and for

the female group 39.2 ± 7.8 units (p < 0.05). The patients had similar diets, physical activity and BMI. After 2 weeks, we measured the total daily insulin requirements. For the male group, the total daily dose of insulin decreased from 34.5 ± 8.4 to

24.3 ± 2.8 units and for the female group from 39.2

±7.8 to 27.8 ± 6.9 units (Figure 7) (p < 0.01)

The mean glycemia decreased in the female group from 174.4 ± 11.6 mg/dL to 122.5 ±

11.4 mg/dL and in the male group from 168.5 ±

12 mg/dL to 130.5 ± 10.2 mg.dL (Figure 8).

from 168.5 ± 12 mg/dL to 130.5 ± 10.2 mg.dL (Figure 8). Figure 1. Decrease of

Figure 1. Decrease of the HOMA-IR in the female group (215 pts.).

3

A new pharmacologic agent

235

3 A new pharmacologic agent 235 Figure 2. Decrease of the HOMA-IR in the male group

Figure 2. Decrease of the HOMA-IR in the male group (201 pts.).

2. Decrease of the HOMA-IR in the male group (201 pts.). Figure 3. Further decrease of

Figure 3. Further decrease of the HOMA-IR in 5 women that continued Gerovital H3 treatment for another week.

continued Gerovital H 3 treatment for another week. Figure 4. Further decrease of the HOMA-IR in

Figure 4. Further decrease of the HOMA-IR in 5 men that continued Gerovital H3 treatment for another week.

236

T. Mogoş et al.

4

236 T. Mogoş et al . 4 Figure 5. Decrease in IR in the female group
236 T. Mogoş et al . 4 Figure 5. Decrease in IR in the female group
236 T. Mogoş et al . 4 Figure 5. Decrease in IR in the female group

Figure 5. Decrease in IR in the female group after 2w and 3w of treatment with Gerovital ® H3 .

after 2w and 3w of treatment with Gerovital ® H 3 . Figure 6. Decrease in
after 2w and 3w of treatment with Gerovital ® H 3 . Figure 6. Decrease in
after 2w and 3w of treatment with Gerovital ® H 3 . Figure 6. Decrease in

Figure 6. Decrease in IR in the male group after 2w and 3w of treatment with Gerovital ® H3 .

after 2w and 3w of t reatment with Gerovital ® H 3 . Figure 7. Decrease

Figure 7. Decrease of the total daily insulin requirements after treatment with Gerovital® H3 .

5

A new pharmacologic agent

237

5 A new pharmacologic agent 237 Figure 8. Decrease of the glycaemic levels after treatment with

Figure 8. Decrease of the glycaemic levels after treatment with Gerovital ® H3 .

DISCUSSION

From the results presented in the context of treatment with Gerovital ® H3 we seem to have found a new method to reduce the IR. From the clinical practice point of view, having used plenty of anti-IR agents and not having reached the results we were expecting, we are looking for other opportunities in order to achieve our target [6,7]. In this way, the Gerovital ® H3 seems to be an optimal solution, even if the effect lasts only for a short period of time (weeks). We observed that patients with IR and unbalanced diabetes could have a benefit from the Gerovital ® H3 therapy, by reducing IR and by balancing the glycaemic levels and insulin requirements. Until now we could not find a realistic mechanism to explain the reduction in IR after this kind of treatment. There are different opinions on this subject. We shall mention only some of them: a reduction in apoptosis, activation of lipoprotein- lipase, a better vascularization of tissues (it is known that this reduces IR) and a better stimulation of the beta-cell activity [8–10]. It is possible that the component in Gerovital ® H3 improves the function of the central nervous system and by these means decreases the response in catecholamines and glucocorticoids in the peripheral area. It is well known that these hormones act in opposite manner to insulin, resulting in increased IR [12,13]. The fact that IR increases with age could be another medical indication for the use of this product [14].

We should take into account that Gerovital ® H3 should be administered periodically [15], so that its effect on reducing IR can be maintained over a long period of time. On the other hand, we must stress that the pathological conditions associated with age could be improved if the patients take several periodical cures of Gerovital [16,17]. From our clinical experience, we are convinced that the more the Gerovital ® H3 is given in a cure, the bigger the decrease in IR is observed. An interesting fact we noticed was that women respond better to the treatment when compared to men, even if their BMI is a bit greater than that of males (30.2 ± 1.8 vs. 28.9 ± 1.5).

CONCLUSION

1. We found a new agent that improves insulin resistance. 2. It is a good therapeutic solution for those especially situated in the geriatric area. 3. The degree of limiting of IR seems to be more evident in women that in men. 4. The beneficial aspect of reducing IR can be used in plenty of syndromes associated with IR, such as metabolic syndrome, diabetes mellitus, dyslipidemia, arterial hypertension and acute coronary syndromes. 5. The action of Gerovital ® H3 continues weeks after the end of treatment.

238

T. Mogoş et al.

6

Insulinorezistenţa este piatra de temelie a mai multor afecţiuni, cum ar fi sindromul metabolic, diabetul zaharat, hipertensiunea arterială, dislipidemia, sindromul coronarian acut etc. Există unele medicaţii, dar şi unele schimbări ale stilului de viaţă care pot altera rezistenţa la insulină. Nu toate aceste modalităţi sunt potrivite pentru toţi pacienţii. Noi am descoperit un alt medicament care poate fi adăugat cu success celorlalte metode mai vechi de reducere a insulinorezistenţei.

Corresponding author: T. Mogos “Prof. Dr. N.C. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases E-mail: tibimogos@yahoo.com

REFERENCES

1. ZULIANI G, MORIERI ML, VOLPATO S, MAGGIO M, CHERUBINI A, FRANCESCONI D, BANDINELLI S , PAOLISSO G, GURALNIK JM, FERRUCCI L. Insulin resistance and systemic inflammation, but not metabolic syndrome phenotype, predict 9 years mortality in older adults. Atherosclerosis. 2014 Aug; 235(2):538–45.

2. ZULIANI G, VOLPATO S, GALVANI M, BLÈ A, BANDINELLI S, CORSI AM, LAURETANI F, MAGGIO M, GURALNIK JM, FELLIN R, FERRUCCI L. Elevated C-reactive protein levels and metabolic syndrome in the elderly: The role of central obesity data from the InChianti study. Atherosclerosis. 2009 Apr; 203(2):626–32.

3. ONAT A, HERGENÇ G, TÜRKMEN S, YAZICI M, SARI I, CAN G. Discordance between insulin resistance and metabolic syndrome: features and associated cardiovascular risk in adults with normal glucose regulation. Metabolism. 2006 Apr;

55(4):445–52.

4. REAVEN GM. Insulin resistance, the insulin resistance syndrome, and cardiovascular disease. Panminerva Med. 2005 Dec;

47(4):201–10.

5. REAVEN G, ABBASI F, MCLAUGHLIN T. Obesity, insulin resistance, and cardiovascular disease . Recent Prog Horm Res. 2004; 59:207–23.

6. MCLAUGHLIN T, ABBASI F, CHEAL K, CHU J, LAMENDOLA C, REAVEN G. Use of metabolic markers to identify overweight individuals who are insulin resistant. Ann Intern Med. 2003 Nov 18; 139(10):802–9.

7. MOGOS T. Metabolic urgency. Ed. Enciclopedica, Bucuresti, 1992.

8. WILLETTE AA, JOHNSON SC, BIRDSILL AC, SAGER MA, CHRISTIAN B, BAKER L, CRAFT S, OH J, STATZ E, HERMANN BP, JONAITIS EM, KOSCIK RL, LA RUE A, ASTHANA S, BENDLIN BB. Insulin resistance predicts brain amyloid deposition in late middle-aged adults. Alzheimers Dement. 2014 Jul 17. pii: S1552-5260(14)02420–0.

9. RYAN AS, GE S, BLUMENTHAL JB, SERRA MC, PRIOR SJ, GOLDBERG AP. Aerobic exercise and weight loss reduce vascular markers of inflammation and improve insulin sensitivity in obese women. J Am Geriatr Soc 2014 Apr; 62(4):607–14.

10. NG TP, FENG L, YAP KB, LEE TS, TAN CH, WINBLAD B. Long-term metformin usage and cognitive function among older adults with diabetes. J Alzheimers Dis.2014; 41(1):61–8.

11. HADI HA, SUWAIDI JA. Endothelial dysfunction in diabetes mellitus. Vasc Health Risk Manag. 2007; 3(6):853–76.

12. TANASHIAN MM, LAGODA OV, ORLOV SV, TELENKOVA NG, MAKSIUTKINA LN, PETRUKHINA SIU. Cerebro- vascular diseases and metabolic syndrome. Ter Arkh. 2013; 85(10):34–42.

13. KUROSE S,TSUTSUMI H,YAMANAKA Y, SHINNO H, MIYAUCHI T, TAMANOI A, IMAI M, MASUDA I, KIMURA Y. Improvement in endothelial function by lifestyle modification focused on exercise training is associated with insulin resistance in obese patients. Obes Res Clin Pract.2014 Jan–Feb; 8(1):e106–114.

14. FANG FS, LIU MY, CHENG XL, ZHONG WW, MIAO XY, LI J, LI CL, TIAN H. Insulin resistance correlates with the arterial stiffness before glucose intolerance. Intern Med. 2014; 53(3):189–94.

15. HANYU H. Diabetes mellitus and dementia. Brain Nerve. 2014 Feb; 66(2):129–34.

16. WHITMER RA. Type 2 diabetes and risk of cognitive impairment and dementia. Curr Neurol Neurosci Rep. 2007 Sep;

7(5):373–80.

17. MENG C, SUN M, WANG Z, FU Q, CAO M, ZHU Z, MAO J, SHI Y, TANG W, HUANG X, DUAN Y, YANG T. Insulin Sensitivity and Beta-Cell Function Are Associated with Arterial Stiffness in Individuals without Hypertension. J Diabetes Res 2013; 2013:151675.

Received September 28, 2014