Skip to main content

Residual β-cell function in Brazilian Type 1 diabetes after 3 years of diagnosis: prevalence and association with low presence of nephropathy



Persistence of β cell-function in Type 1 diabetes (T1D) is associated with glycaemia stability and lower prevalence of microvascular complications. We aimed to assess the prevalence of residual C- peptide secretion in long-term Brazilian childhood onset T1D receiving usual diabetes care and its association to clinical, metabolic variables and microvascular complications.


A cross-sectional observational study with 138 T1D adults with ≥ 3 years from the diagnosis by routine diabetes care. Clinical, metabolic variables and microvascular complications were compared between positive ultra-sensitive fasting serum C-peptide (FCP +) and negative (FCP-) participants.


T1D studied had ≥ 3 yrs. of diagnosis and 60% had FCP > 1.15 pmol/L. FCP + T1D were older at diagnosis (10 vs 8 y.o; p = 0.03) and had less duration of diabetes (11 vs 15 y.o; p = 0.002). There was no association between the FCP + and other clinical and metabolic variable but there was inversely association with microalbuminuria (28.6% vs 13.4%, p = 0.03), regardless of HbA1c. FCP > 47 pmol/L were associated with nephropathy protection but were not related to others microvascular complications.


Residual insulin secretion is present in 60% of T1D with ≥ 3 years of diagnosis in routine diabetes care. FCP + was positively associated with age of diagnosis and negatively with duration of disease and microalbuminuria, regardless of HbA1c.


Type 1 diabetes (T1D) is an autoimmune disease characterized by progressive destruction of β cells that begins long before and continues long after the clinical diagnosis, as believed. It occurs at different rates among individuals, with some demonstrating long residual insulin secretion. There are controversies about the various factors related to the persistence of residual C-peptide secretion in T1D such as genetic, duration of diabetes and age at diagnosis among others. Ethnicity, for instance, might have influenced the rate of β cell loss after diagnosis since Hispanics had shown higher fasting C-peptide at the beginning of Trial Net New Onset Intervention Trials [1].

The importance of residual insulin secretion was already highlighted in the DCCT study (Diabetes Control and Complications Trial) in which participants with stimulated C-peptide higher than 200 nmol/L had better glycemic control, lower risk of hypoglycemia and lower risk of diabetes chronic complications [2, 3].

Classically chronological age, age at T1D diagnosis, duration of T1D, average systolic blood pressure and HbA1c are associated with chronic diabetic complications, but the relation of latter with residual β-cell function has been shown heterogenous results [4,5,6,7], besides there is great evidence that C-peptide counteracts the detrimental changes causes by hyperglycemia at the cellular level in animal studies [8].

On the other side, there has no sufficient data about residual β cell function in long duration Brazilian T1D by routine diabetes care as in developing countries with a heterogeneous genetic population. These would help revealing the complex natural history of the disease considering its heterogeneity among different populations.

Therefore, the study aimed to assess the prevalence of residual C- peptide secretion, its association with clinical characteristics, and its impact on microvascular complication in Brazilian childhood onset T1D.

Research design and methods

Study participants

This is a cross-sectional observational study of 138 Brazilian people with T1D with more than 3 years of duration, selected from electronic medical records between 2014 to 2018 that had realized ultrasensitive C-peptide assay.

Inclusion criteria: Individuals recruited from the Diabetes Center—Federal University São Paulo (Southeast Brazil) with Type 1 diabetes (ADA criteria as continuous use of insulin since diagnosis, positive ketones, and presence of pancreatic autoantibodies).

Exclusion criteria: Hepatic disease, Chronic renal insufficiency or clinical characteristics suggesting another type of diabetes mellitus.


The data analyzed were age (years), age at diagnosis of T1D (years), time of diagnosis of diabetes (years), sex, body mass index {BMI (Kg/m2)}, arterial hypertension (SBP > 130 mmHg e DBP > 90 mmHg, or > P95 for age), Total Cholesterol HDL-c (mg/dl), LDL-c (mg/dl), Triglycerides (TG)(mg/dl), TSH (mU/ml) and free T4(ng/ml), HbA1c (HPLC—high-performance liquid chromatography—normal range 20–38 mmol/mol; 3.5 a 5.6%), and albumin excretion—Cobas Mira® Roche (AlbUCobas—NV < 17 mg/L or 30 mg/24hs).

The ultrasensitive C-peptide assay used was the Mercodia® ELISA (Uppsala, Sweden, cat. No. 10-1141-01) whose detection limit is 1.15 pmol/L, with an inter-and intra-assay coefficient of variation of 5.5% and 3.8%, for a C-peptide at 37 pmol / L. Participants whose FCP was greater than 1.15 pmol/L were classified as positive (FCP +) and below this value as negative (FCP-).

The presence of microvascular complications was taken derived of data from the electronic medical records and was fundoscopy for retinopathy, DCCT clinical exam protocol for neuropathy, microalbuminuria (in 2 of 3 albumin to creatinine ratios high > 30 mg/ml) for nephropathy and the evaluation of hypoglycemia was performed according to the frequency of file reported hypoglycemia.

Statistical analyses

Normally distributed data were presented as mean SD and variable with skewed distribution were reported as median with interquartile ranges (25th,75th). Categorical variables are expressed as absolute frequency and percentage.

For the comparisons of two groups in continuous variables, the t-student test was used depending on the normality assumption (tested by the Anderson–Darling test) and for the others, the Mann–Whitney nonparametric test was used. Fisher’s exact tests were used for categorical variables. Simple and multiple logistic regression models were used to analyze the associations between the outcome variables. Statistics C was used to evaluate the model.

We applied a multivariable logistic regression model using complications event as the binary dependent variable and C-peptide as the independent variable. The duration-adjusted comparisons were represented by the P-value and odds ratio of the C-peptide term in the multivariable model. Scatter plots and bar plots were used to illustrate the distribution of variables. The level of significance was 0.05. Two-tailed hypotheses were considered. Software R version 3.6.0 was used to perform all analyzes.


One hundred and thirty-eight participants (58.7% men) were evaluated and 59.5% of them was FCP + (> 1.15 pmol/L). The means age (sd) at T1D diagnosis was 9.0 ± 0.47 years and by the time of the study was 22.0 ± 0.6 years. Diabetes duration of 12.0 ± 0.5 years and the mean HbA1c was 8.35 ± 1.15% (67 ± 1.6 mmol/mol). Clinical, endocrine, and metabolic characteristics of the participants and the frequency of dyslipidemia and diabetic microvascular complications are shown in Table 1.

Table 1 Clinical, endocrine, and metabolic characteristics of T1D participants

We observed that there was a statistically significant positive association between FCP + and age at T1D diagnosis (p = 0.039) and negative association (p = 0.002) with disease duration.

From the regression data, the probability most participants having FCP + with a diabetes duration of 5 years would be about 75%, in 10 years 64.5% and in 20 years less than 50% (Fig. 1). Also, these data shown that each time unit increase of diabetes duration(years) correspond to 8% reduction (OR = 0.92) in the probability of having FCP + .

Fig. 1
figure 1

Fasting C-peptide levels according to diabetes duration in the T1D participants. The dashed horizontal line across the entire lower portion of the panel displays the limit of detection (1.15 pmol/L)

There was no association between the presence of FCP and clinical (age and BMI) and metabolic variables (current HbA1c, LDL-c and TG) by the time of the study.

In a regression model adjusted for covariates, we found a lower prevalence (13.4%) of albuminuria among participants with FCP + compared to 27those with FCP- (28.6%, p = 0.031). Simple logistic regression showed that participants without nephropathy were 2.5 times more likely to have FCP + than those with this microangiopathy.


This study showed for the first time, that using an ultrasensitive method for serum C-peptide, around 60% of long-term Brazilian T1D with childhood-onset (~ 17 yrs of diabetes duration) had residual insulin secretion. These detectable FCP levels was associated with older age at T1D diagnosis and shorter diabetes duration. Importantly this group with even low levels of residual C-peptide had lower prevalence of microalbuminuria adjusted for diabetes duration and HbA1c levels.

The decline of C-Peptide in T1D during the first years (in general three years) as reported in the literature is highly variable [9]. After this period patient become non-C-peptide secretor or low C-peptide secretor, which is more evident and prevalent when using ultra-sensitive C-peptide assays [10]. Most studies evaluating C-peptide in people with long-standing diabetes, included T1Ds with more than 3–5 years of duration, like one from Prof. Greenbaum group (an expert in this area) which use as an eligibility criteria of ages from 6 months to 46 years and diabetes duration of more than 3 years [5]. Others, such as the pioneering study by Denise Faustman [10], stratified by six intervals of disease duration included participants from 0 to more than 40 years duration. This is precisely why it has been studied in recent years, the persistence of prolonged C-peptide production and lower risk of complications, and that people diagnosed in adulthood have more insulin reserve than diagnosed in childhood. [11]. And a more recent study considered T1D individuals with diabetes duration with more than 5 years to evaluate C-peptide and complications [12]. Therefore, we selected participants with more than 3 years of diagnosis, but with an average diabetes duration time of 17 years, thus subject to the risk of complications. [13], mainly in our country where the T1D glycemic control legacy is not very good. However, the role of diabetes duration on fasting C-peptide in these patients was extensively studied and the probability of being C-peptide negative at 15 years of diagnosis is 45%, 20 years is 56%, 25 years 66%, 30 years is 75% and 40 years is 89%.

Preliminary studies, from UK Golden Years cohort [14], the 50-year Joslin Medalist study [15], and the Parisian cohort [16] have examined the clinical characteristics of type 1 diabetic patients with long disease duration. Subsequently, Joslin’s group further explored the data to evaluate possible markers of longevity without significant complications, including evaluation of C-peptide and some pancreatic histology. They showed that most of them could produce insulin endogenously (67% with standard C-peptide assay > 0.03 nmol/L) and confirm the presence of insulin in some available Medalist pancreases. [17] It is important to point out that many Medalists had monogenic diabetes variants that potentially contribute to heterogeneity of beta cell function in this group of patients.

In recent years, the development of an ultrasensitive assay for plasma C-peptide detection (change the lower limits of detection of approximately 50 pmol/L to levels as low as 1.15 pmol/L) has made it possible to detect residual secretion of β-cell function in people with T1D, even after decades of disease [18,19,20]. The percentage of residual FCP that we found is five times higher than the 13.2% found in a group of adults with T1D with a shorter disease time when using a regular C-peptide assay in routine clinics [21].

Studies with similar characteristics to our group, found 55–66% positivity (lower limit of 1.15 pmol/L for fasting serum C-peptide) and 52% for urinary C- peptide (> 30 pmol/L) [11, 15, 22] while others like participants of Exchange Clinic Network found detectable C-peptide in 29% among 900 participants, suggesting that residual C-peptide secretion is present in almost one out of three T1D individuals, three or more years from diabetes diagnosis [5]. (Table 2).

Table 2 Comparation of positive C-peptide among different studies using ultra-sensitive assay

According to our analysis, we verified that one of the main factors related to the frequency of FCP considered positive (> 1.15 pmol/L) were age at diabetes diagnosis and the duration of the disease. These two factors, also shown in our population, are in according to other groups where age at the diagnosis was positively associated with C-peptide values [5, 10, 22]. The relationship between age at T1D diagnosis and residual C-peptide can be explained by different insulin profiles found at diagnosis as it has been shown in new onset teenage T1D that still retain approximately 40% of residual insulin-containing islets [21].

In our population each increase of one year of age correspond to 8% reduction (OR = 0.92) in probability of having FCP + . It would be expected better values ​​in our patients than the English and American ones which had longer disease duration, however our patients presented a marginally lower prevalence of residual C-peptide secretion [15, 17]. In addition, detectable C-peptide related to better A1c was found in 38% of children and adolescents after 10 years of diabetes compared to 24% of our patients as they are from public care services. Insufficient metabolic control may have contributed to this result. However, a recent systematic review and meta-analyses of all randomized controlled trials (RCTs) to preserve β-cell function in people with newly diagnosed T1D shown there is a lack of robust evidence that interventions to improve glucose control preserve β-cell function and efforts to treatment algorithms should be a priority [22].

However, one major debate today is what C-peptide level is clinically useful. In part because some studies that correlated residual C-peptide to chronic diabetes complications or hypoglycemia sometimes measure FCP [19, 23, 24] sometimes use stimulated C-peptide [21] besides the sensibility limit of ultra-sensitivity C-peptide assay used [23].

In our T1D participants with a mean 17 years of disease duration, using a C-peptide assay with a limit of sensibility of 1.15 pmol/L we did not find any association between residual C-peptide and lower HbA1c. This agrees with studies with similar T1D populations, while Trial net participants and T1D from the UNITED Team found this association only during the early course of diabetes [23, 25, 26]. Also, a recent work with young adult T1D with 5 years of diabetes duration demonstrated that only those with high levels of residual C-peptide (peak after stimulus test > 4.0 pmol/L or > 1.2 ng/mL) shown β cell responsiveness to hyperglycemia and likely contribute to glycemic control [25]. We have studied β cell responsiveness to sulfonylurea test in a sample of nine patients with FCP + and found that the maximum peak during the test was 0.286 pmol/L (data not shown) which is approximately 93% less than shown in the study above [27]. This might help understanding why we do not get an association between C-peptide levels and HbA1c in our T1D group and why we did no find significant difference in the prevalence of hypoglycemia between our FCP + and FCP- groups. Nevertheless, heterogeneous relationship between the glucagon response to insulin-induced hypoglycemia does exist but again is most evident in T1D with high levels of residual C-peptide [25].

In relation to diabetes chronic complications and residual C-peptide in our study using FCP with limit of sensibility of the assay equal 1.15 pmol/L, we found an inverse relationship between the C-peptide reserve and albuminuria in FCP + T1D patients.

The frequency of albuminuria found in our participants was like people with T1D described in the literature with the same time of disease (19.6% vs 14.8%) where 65.2% of microalbuminuric patients had no detectable C-peptide. However, unlike predicted, we found no correlation of C-peptide and retinopathy, perhaps because of the low prevalence found in our participants (3.9% vs 9–40%) [28]. Also, maybe the low cut-off limit we used to define FCP + patients.

The classical work that found C-peptide protection from complications as nephropathy, neuropathy and retinopathy considered FCP levels > 10 pmol/L (with the same C-peptide assay that we used) almost 9 times higher than our C-peptide cut-off. Other study [20] using the same cut-off value of ours (1.15 pmol/L) also did not find relation among residual C-peptide and retinopathy, neuropathy but marginally lower macroalbuminuria in those with detectable levels (23.4% vs 0%, p = 0.07). A larger sample size might have allowed a bigger difference [25].

One point for discussion is why these low levels of C-peptide can decrease the prevalence of nephropathy, regardless to HbA1c level but not the two others microangiopathies (retinopathy and neuropathy).

Diabetic nephropathy (DN) is one of the major microvascular complications, present in 20 to 40% of T1D people and is one of the most important causes of kidney failure (KF), but the rate of renal decline varies widely among them. On the other hand, in addition to its well-known role as a biomarker of functional beta-cell mass, the C-peptide is a bioactive molecule with physiological effects on peripheral cell targets and with antioxidant protection on vascular endothelial. Small trials in which C-peptide was given to subjects with T1D with nephropathy or neuropathy showed that C-peptide mitigates renal and neuronal complications [30, 31], while others had shown that C-peptide can suppress various molecular mechanisms involved in the pathophysiology of DN and therefore could prevent the onset and progression of KF [32]. Interestingly almost two decades ago, a double-blind randomized study had demonstrated that administration of biosynthetic human C-peptide plus insulin reduced glomerular permeability and urinary excretion of albumin [33].

In relation to the lower prevalence of DN in our FCP + T1D regardless of the same HbA1c as FCP- ones, we can speculate that the former could have less glycemic variability. Since recent works have been shown that for every 100 pmol/L increases in C-peptide peak the percentage of time spent in the range (70–180 mg/dl) increased by 2.4% with a reduction in time spent at level 1 hyperglycemia (> 180 mg-dl) and level 2 hyperglycemia (250 mg-dl) by 2.6% and 1.3% respectively [34]. Is important to mention that lower time in range was associated with presence of composite microvascular complications in recent study with a group of adults with long T1D duration [34].

When we studied the relationship between C-peptide levels and nephropathy in our T1D group we found out that all patients with fasting C-peptide ≥ 46.9 pmol/L (0.14 ng/ml) were negative for this microangiopathic complication. This number is close to cut-off used in most studies (50 pmol/L but one that considered 10 pmol/) [33] for identify patients at higher risk for complications, more frequent and great glycemic excursions and low 1,5 AG levels.

Finally, at this level of glycemic control, we did not find difference on lipid profile between T1D patients with and without residual C-peptide. However, results in this area are heterogenous, some works showing better lipid profile in C-peptide positive and others showing no relationship between unstimulated C-peptide values and lipid parameters in either remitters or non-remitters T1D adult [35].

The present study has some limitations as the small sample size, the cross-sectional data, using FCP although the literature has already shown a good correlation with stimulated C-peptide. Another limitation was the low prevalence of chronic diabetes complications that may have impaired the association studies. The strengths were the assay sensitivity, the heterogenous genetic background of our T1D population and the real-world data from their routine treatment.

We can conclude that most of our T1D participants, like American and European data, have residual beta-cell function demonstrated with the use of an ultrasensitive assay after a decade of disease, and this minimal detectable C-peptide appears to protect against albuminuria regardless of HbA1c.

Finally, the importance of persistent beta-cell residual function reinforces strategies for its preservation since diagnosis and suggests that a significant percentage of patients with T1D, even after decades of diagnosis, may have benefits in slowing the development of diabetes nephropathy.

Availability of data and materials

All data are available.



Type 1 Diabetes

HbA1c :

Glycated Hemoglobin A1c


Body Mass Index


Systolic blood pressure


Diastolic blood pressure




  1. Tosur M, Cleves MA, Sosenko JM, et al. The effect of ethnicity in the rate of beta-cell functional loss in the first 3 years after type 1 diabetes diagnosis. J Clin Endocrinol Metab. 2020;105:e4393–406.

    Article  PubMed  PubMed Central  Google Scholar 

  2. The DCCT Research Group. Effects of age, duration, and treatment of insulin-dependent diabetes mellitus on residual beta-cell function: observations during eligibility testing for the Diabetes Control and Complications Trial (DCCT). J Clin Endocrinol Metab. 1987;65:30–6.

    Article  Google Scholar 

  3. Steffes MW, Sibley S, Jackson M, et al. Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial. Diabetes Care. 2003;26:832–6.

    Article  PubMed  Google Scholar 

  4. Panero F, Novelli G, Zucco C, et al. Fasting plasma C-peptide and micro-and macrovascular complications in a large clinic-based cohort of Type 1 diabetic patients. Diabetes Care. 2009;32:301–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Davis AK, DuBose SN, Haller MJ, et al. Prevalence of detectable C-peptide according to age at diagnosis and duration of Type 1 diabetes. Diabetes Care. 2015;38:476–81.

    Article  CAS  PubMed  Google Scholar 

  6. Lachin JM, McGee P, Palmer JP, DCCT/EDIC Research Group. Impact of C-peptide preservation on metabolic and clinical outcomes in the Diabetes Control and Complications Trial. Diabetes. 2014;63:739–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Nakanishi K, Watanabe C. Rate of beta-cell destruction in Type 1 diabetes influences the development of diabetic retinopathy: protective effect of residual beta-cell function for more than 10 years. J Clin Endocrinol Metab. 2008;93:4759–66.

    Article  CAS  PubMed  Google Scholar 

  8. Ryk A, Tosiewicz A, Michalak A, et al. Biological activity of C-peptide in microvascular complications of Typ1 diabetes—time for translational studies or back to the basics? Int J Mol Sc. 2020;21:9723.

    Article  CAS  Google Scholar 

  9. Palmer JP. C-peptide in the natural history of Type 1 Diabetes. Diabetes Metab Res Ver. 2009;25:325–8.

    Article  CAS  Google Scholar 

  10. Wang L, Lovejoy NF, Faustman DL. Persistence of prolonged C-peptide production in type 1 diabetes as measured with an ultrasensitive C-peptide assay. Diabetes Care. 2012;35:465–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Oram RA, Jones AG, Besser REJ, et al. The majority of patients with long-duration type 1 diabetes are insulin microsecretors and have functioning beta cells. Diabetologia. 2014;57:187–91.

    Article  CAS  PubMed  Google Scholar 

  12. Vollenbrock CE, Mul D, Dekker P, Birnie E, Vries-Velraeds MMC, et al. Fasting and meal -stimulated serum C-peptide in long-standing type 1 diabetes mellitus. Diabet Med. 2023;40:e15012.

    Article  CAS  PubMed  Google Scholar 

  13. Hao W, Gitelman S, DiMeglio LA, et al. Type 1 Diabetes TrialNet Study Group. Fall in C-peptide during first 4 years from diagnosis of type 1 diabetes: variable relation to age, HbA1c, and insulin dose. Diabetes Care. 2016; 39:1664–70.

  14. Bain SC, Gill GV, Dyer PH, et al. Characteristics of type 1 diabetes of over 50 years duration (the Golden Years Cohort). Diabet Med. 2003;20:808–11.

    Article  CAS  PubMed  Google Scholar 

  15. Keenan HA, Costacou T, Sun JK, et al. Clinical factors associated with resistance to microvascular complications in diabetic patients of extreme disease duration: the 50-year Medalist study. Diabetes Care. 2007;30:1995–7.

    Article  CAS  PubMed  Google Scholar 

  16. Feldman-Billard S, Limon S, Morin Y, Altman JJ. Type 1 diabetes with no diabetic complications, sixty-two years later. J Diabetes Complications. 2001;15:285–6.

    Article  CAS  PubMed  Google Scholar 

  17. Keenan HA, Sun JK, Levine J, Doria A, Aiello LP, Eisenbarth G, Bonner-Weir S, King GL. Residual insulin production and pancreatic -cell turnover after 50 years of diabetes: Joslin Medalist Study. Diabetes. 2010;59:2846–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Greenbaum CJ, Harrison LC, Immunology of Diabetes Society. Guidelines for intervention trials in subjects with newly diagnosed type 1 diabetes. Diabetes. 2003;52:1059–65.

    Article  CAS  PubMed  Google Scholar 

  19. Kuhtreiber WM, Washer SLL, Hsu E, et al. Low levels of C-peptide have clinical significance for established Type 1 diabetes. Diabet Med. 2015;32:1346–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Fotinopoulos E, Clarke CAL, Pattenden RJ, et al. Impact of routine clinic measurement of serum C-peptide in people with a clinician-diagnosis of type 1 diabetes. Diabet Med. 2021;38: e14449.

    Google Scholar 

  21. Leete P, Willcox A, Krogvold L, et al. Differential insulinic profiles determine the extent of β-cell destruction and the age at onset of type 1 Diabetes. Diabetes. 2016;65:1362–9.

    Article  CAS  PubMed  Google Scholar 

  22. Narendran P, Tomlinson C, Beese S, et al. A systematic review and meta-analysis of interventions to preserve insulin -secreting β-cell function in people with type 1 diabetes: results from intervention studies aimed at improving glucose control. Diabet Med. 2022;39: e14730.

    Article  CAS  PubMed  Google Scholar 

  23. Williams KV, Becker DJ, Orchard TJ, et al. Persistent C-peptide levels and microvascular complications in childhood onset type 1 diabetes of long duration. J Diabetes Complicat. 2019;33:657–61.

    Article  Google Scholar 

  24. Cheng J, Yin M, Tang X, et al. Residual β-cell function after 10 years of autoimmune type 1 diabetes: prevalence, possible determinants, and implications for metabolism. Ann Transl Med. 2021;9:650.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Marren SM, Hammersley S, McDonald TJ, et al. Persistent C-peptide is associated with reduced hypoglycaemia but not HbA1c in adults with longstanding Type 1 diabetes: evidence for lack of intensive treatment in UK clinical practice? Diabet Med. 2019;36:1092–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gubitosi-Klug RA, Braffett BH, Hitt S, et al. Residual β cell function in long-term type 1 diabetes associates with reduced incidence of hypoglycemia. J Clin Invest. 2021;131: e143011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Rickels MR, Evans-Molina C, Bahnson HT, et al. High residual C-peptide likely, contributes to glycemic control in type 1 diabetes. J Clin Invest. 2020;130:1850–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Tomislav B, Tomic M, Vuckovic-Rebrina S, et al. Preserved C-peptide secretion in patients with type 1 diabetes and incipient chronic complications is associated with lower serum resistin and higher uric acid levels. J Diab Metab Dis. 2020;19:1185–9.

    Article  Google Scholar 

  29. Oram RA, McDonald TJ, Shields BM, et al. Most people with long-duration type 1 diabetes in a large population-based study are insulin microsecretors. Diabetes Care. 2015;38:323–8.

    Article  CAS  PubMed  Google Scholar 

  30. Johansson BL, Borg K, Fernqvist-Forbes E, et al. Beneficial effects of C-peptide on incipient nephropathy and neuropathy in patients with Type 1 diabetes mellitus. Diabet Med. 2000;17:181–9.

    Article  CAS  PubMed  Google Scholar 

  31. Brunskill NJ. C-peptide and diabetic kidney disease. J Intern Med. 2017;281:41–51.

    Article  CAS  PubMed  Google Scholar 

  32. Johansson BL, Kernell A, Sjöberg S, et al. Influence of combined C-peptide and insulin administration on renal function and metabolic control in diabetes type 1. J Clin Endocrinol Metab. 1993;77:976–81.

    CAS  PubMed  Google Scholar 

  33. Malahi AE, Van Elsen M, Charleer S, et al. Relationship between Time in Range, Glycemic variability, HbA1c, and complications in adults with Type 1 diabetes. J Clin Endocrinol Metab. 2022;107:e570–81.

    Article  PubMed  Google Scholar 

  34. Zhang L, Xu Y, Jiang X, et al. Impact of flash glucose monitoring on glycemic control varies with the age and residual β-cell function of patients with type 1 diabetes mellitus. J Diabetes Investig. 2022;13:552–9.

    Article  CAS  PubMed  Google Scholar 

  35. Nwosu BU, Parajuli S, Khatri K, et al. Partial clinical remission reduces Lipid-based cardiovascular risk in adult patients with Type 1 diabetes. Front Endocrinol. 2021;12: 706555.

    Article  Google Scholar 

Download references


The authors thank all study participants.


No funding has been received.

Author information

Authors and Affiliations



MALG and SAD responsible to the conception and design, acquisition of data, or analysis and interpretation of data. FC did C-peptide analyses. All authors participated in drafting the article or revising it and approved the final version of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Monica A. L. Gabbay.

Ethics declarations

Ethics approval and consent to participate

The study was approved by the Teaching and Research Commission of the Federal University of São Paulo and the Medical Ethics Committee (Protocol # 2015/05345-1) based on the ethical principles in accordance with the Declaration of Helsinki.

Competing interests

No author has a competing interest related to the work described in this paper.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gabbay, M.A.L., Crispim, F. & Dib, S.A. Residual β-cell function in Brazilian Type 1 diabetes after 3 years of diagnosis: prevalence and association with low presence of nephropathy. Diabetol Metab Syndr 15, 51 (2023).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: